The U.S. Food and Drug Administration issued warning letters to seven companies for illegally selling dietary supplements that claim to cure, treat, mitigate or prevent cardiovascular disease or related conditions, such as atherosclerosis, stroke or heart failure, in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The FDA is urging consumers not to use these or similar products because they have not been evaluated by the FDA to be safe or effective for their intended use and may be harmful.
The warning letters were issued to:
- Essential Elements (Scale Media Inc.);
- Calroy Health Sciences LLC;
- BergaMet North America LLC;
- Healthy Trends Worldwide LLC (Golden After 50);
- Chambers’ Apothecary;
- Anabolic Laboratories, LLC.
“Given that cardiovascular disease is the leading cause of death in the U.S., it’s important that the FDA protect the public from products and companies that make unlawful claims to treat it. Dietary supplements that claim to cure, treat, mitigate or prevent cardiovascular disease and related conditions could potentially harm consumers who use these products instead of seeking safe and effective FDA-approved treatments from qualified health care providers,” said Cara Welch, Ph.D., director of the Office of Dietary Supplement Programs in the FDA’s Center for Food Safety and Applied Nutrition. “We encourage consumers to remain vigilant when shopping online or in stores to avoid purchasing products that could put their health at risk.”
Under the FD&C Act, products intended to diagnose, cure, treat, mitigate or prevent disease are drugs and are subject to the requirements that apply to drugs, even if they are labeled as dietary supplements. Unlike drugs approved by the FDA, the agency has not evaluated whether the unapproved products subject to the warning letters announced today are effective for their intended use, what the proper dosage might be, how they could interact with FDA-approved drugs or other substances, or whether they have dangerous side effects or other safety concerns.
The FDA advises consumers to talk to their doctor, pharmacist or other health care provider before deciding to purchase or use any dietary supplement or drug. Some supplements might interact with medicines or other supplements. Health care providers will work with patients to determine which treatment is the best option for their condition.
If a consumer thinks that a product might have caused a reaction or an illness, they should immediately stop using the product and contact their health care provider. The FDA encourages health care providers and consumers to report any adverse reactions associated with FDA-regulated products to the agency using MedWatch or the Safety Reporting Portal.
The FDA has requested responses from the companies within 15 working days stating how they will address the issues described in the warning letters or provide their reasoning and supporting information as to why they think the products are not in violation of the law. Failure to correct violations promptly may result in legal action, including product seizure and/or injunction.
A review conducted in 2015 reported community pharmacists are willing to adopt a professional role in counselling consumers about the appropriate and safe use of so-called alternative medicine (SCAM) but faced multiple barriers in doing so. This current review aimed to update and extend these findings, by identifying studies published since 2015 that reported on pharmacists across any setting.
Eligible studies published between January 01, 2016, and December 31, 2021, were identified across 6 databases (PubMed, Scopus, Web of Science, EMBASE, ScienceDirect and MEDLINE). A grounded theory approach was used to thematically synthesize the data extracted.
A total of 64studies representing pharmacists across 30 countries were included for review. The study designs varied and included:
- cross-sectional surveys (n = 36),
- qualitative studies (n = 14),
- pseudo-patient studies (n = 3).
Eight studies reported on practice and/or bioethical responsibilities and 19 studies documented factors that would enable pharmacists to fulfill these responsibilities, while 37 studies reported on both.
The authors concluded that these findings indicate research about pharmacists’ responsibilities associated with SCAM is evolving from gap analysis towards research that is proactive in advocating for change in multiple areas. These findings can be used to inform a consensus discussion among pharmacists and key stakeholders regarding a set of professional responsibilities that would serve in the development of: a clearly defined role and associated practice standards, and competency requirements that inform educational learning objectives for inclusion in undergraduate, post-graduate and continuing professional pharmacy education.
I am puzzled why so many researchers in this specific area seem to avoid clearer language plainly stating the essential, simple, and undeniable facts. I am equally puzzled why so few pharmacists speak out.
It is obvious that community pharmacists are firstly healthcare professionals and only secondly shopkeepers. As such, they have important professional and ethical duties. Foremost, they are obliged to inform their customers responsibly – and responsible means telling them about the evidence for or against the SCAM product they are about to purchase. This duty also entails that pharmacists must inform themselves about the best current evidence. In turn, this means they must stop tolerating the current plethora of under- or post-graduate SCAM courses that are not evidence-based.
As we have discussed ad nauseam on this blog, none of this is actually happening (except in very few laudable cases)!
By and large, pharmacists continue to go along with the double standards of a) evidence for conventional drugs and b) fairy tales for SCAM. In the interest of progress, patient safety, and public health, it is time that pharmacists wake up and remind themselves that they are not commercially orientated shopkeepers but ethical healthcare professionals.
Camilla spent ten days at the end of October in a sophisticated meditation and fitness center in southern India. Life has recently been hectic for the Queen Consort: at 75, she has been in a non-stop succession of various ceremonies for the funeral of Elizabeth II, always one step behind her husband, not to mention her new status as sovereign… Enough to block her chakras in no time.
She came to the resort with her bodyguards and a handful of friends and was able to take advantage of the tailor-made treatments concocted for her by the master of the house, Dr Issac Mathai, who created this high-end holistic centre on a dozen hectares of scented gardens near Bangalore. The program includes massages, herbal steam baths, yoga, naturopathy, homeopathy, meditation, and Ayurvedic treatments to “cleanse, de-stress, soothe and revitalize the mind, body and soul”, as the establishment’s website states.
Guests are required to follow an individualized, meat-free diet, with organic food from the resort’s vegetable gardens, based on lots of salads or soups – Camilla is said to be a fan of sweet corn soup with spinach. Cigarettes and mobile phones are not allowed, although it is assumed that Camilla must have some privileges due to her status… and the basic rate for the suites, which starts at $950 a night – the price of the rooms varies between $260 and $760, the rate including a consultation with the doctors.
Charles and Camilla have been fans of the Soukya Centre in India for a decade. The place corresponds in every way to their deep-rooted convictions about health. Like her husband, Camilla is a follower of organic food, she also practices yoga and treats her face with creams made from nettle and bee venom. For his part, Charles has long been an advocate of alternative medicine, homeopathy, acupuncture, aromatherapy, and also hypnosis… He even set up a foundation to support complementary medicine by lobbying the British health service to include it in complementary therapies for certain patients, which caused an uproar among the pundits of traditional medicine.
If you suspected I was (yet again) sarcastic about the royal couple, you are mistaken. The text above is only my (slightly shortened) translation of an article published in the French magazine LE POINT (even the title is theirs). I found the article amusing and interesting; so, I looked up the Indian health center. Here are some of the things I found:
The 1st impression is that they are not shy about promotion calling themselves THE WORLD’S BEST AYURVEDA TREATMENT CENTER. The doctor in charge was once a ‘Consultant Physician’ at the Hale Clinic in London, where he treated a number of high-profile people. As his professional background, he offers this:
M.D. (Homeopathy); Hahnemann Post-Graduate Institute of Homeopathy, London M.R.C.H, London; Chinese Pulse Diagnosis and Acupuncture, WHO Institute of Traditional Chinese Medicine, Nanjing, China; Trained (Mind-Body Medicine Programme) at Harvard Medical School, USA
The approach of the center is described as follows:
The fundamental principle underlying Holistic Treatment is that the natural defense and immune system of an individual when strengthened, has the potential to heal and prevent diseases. In the age of super-specialisation where human beings are often viewed as a conglomeration of organs, it is crucial to understand ourselves as multi-dimensional beings with a body, mind and spirit. These interconnected dimensions need to be in perfect harmony to ensure real well-being.
And about homeopathy, they claim this:
Homeopathy originated in 1796 in Germany, and was discovered by Dr. Samuel Hahnemann, a German scientist. Homeopathy is popular today as a non-intrusive, holistic system of medicine. Instead of different medicines for different parts of the body, one single constitutional remedy is prescribed. As a system of medicine, Homeopathy is highly scientific, safe, logical and an extremely effective method of healing. For over 200 years people have used Homeopathy to maintain their good health, and also to treat and cure a wide range of illnesses like allergies, metabolic disorders, atopic dermatitis, Rheumatoid arthritis, Auto-immune disorders.
At this stage, I felt I had seen enough. Yes, you are right, we did not learn a lot from this little exploration. No, hold on! We did learn that homeopathy is highly scientific, safe, logical, and extremely effective!
The question, however, is should we believe it?
The global interest in dieting has increased, and many people have become obsessed with certain fad diets, assuming they are magic bullets for their problems. A fad diet is a popular dietary pattern known to be a quick fix. This review article explores the current evidence related to the health impacts of (amongst others) detox diets (DDs). DDs are interventional diets specifically designed for toxins elimination, health promotion, and weight management. They involve multiple approaches, including total calorie restriction, dietary modification, or juice fasts, and often the use of additional minerals, vitamins, diuretics, laxatives, or ‘cleansing foods’. Some of the many DDs used today are listed below:
|Diet type||Duration||Foods allowed||Proposed claims|
|Liver cleansing diet||8 weeks||Plant-based, dairy-free, low-fat, high-fiber, unprocessed foods are allowed. Epsom salt and liver tonics are also consumed.||Improved energy levels and liver function Toxins removal Improved immune response Efficient metabolism of fats and better weight control|
|Lemon detox diet/Master cleanser||10 days||A liquid-only diet based on purified water, lemon juice, tree syrup, and cayenne pepper. A mild laxative herbal tea and sea salt water is also incorporated.||Toxins removal Shiny hair, glowing skin, and strong nails Weight loss|
|The clean cleanse||21 days||Breakfast and dinner comprise probiotic capsules, cleanse supplements and cleanse shakes. A solid meal in lunch while avoiding gluten, dairy, corn, soy, pork, beef, refined sugars, some fruits, and vegetables.||Toxins removal Improved energy, digestion, sleep, and mental health Reduction in joint pains, headaches, constipation, and bloating|
|Martha’s vineyard detox diet||21 days||Herbal teas, vegetable soups and juices, specially formulated tablets, powders and digestive enzymes are on the menu.||Weight loss Toxins removal Improved energy levels|
|Weekend wonder detox||48 h||Protein-rich meals salads, detox-promoting superfoods, and beverages. Healthy lifestyle, spa treatments, and herbal remedies.||Toxins removal Improved organ function Strengthen body Enhance beauty|
|Fat flush||2 weeks||Large meals are replaced with dilute cranberries, hot water with lemon, pre-prepared cocktails, supplements, and small meals||Toxins removal Reduced stress Weight loss Improved liver function|
|Blueprint cleanse||3 days||Consumption of six pre-prepared vegetable and fruit juices is allowed per day.||Toxins removal|
|The Hubbard purification rundown||Several weeks||Niacin doses along with sustained consumption of vitamin-A, B, C, D, and E. Daily exercise with balanced meals. Restriction of alcohol and drugs. Sitting in a sauna for ≤ 5 h each day.||Toxins removal from fat stores Improved memory and intelligence quotient Better blood pressure and cholesterol levels|
Currently, there is no good clinical evidence for the effectiveness of DDs and some evidence to suggest they might do harm. Many of the DD are liquid-based, low-calorie, and nutrient-poor. For example, a part of BluePrint Cleanse, Excavation Cleanse, provides only 19 g protein and 860 kcal/day which is far below the actual requirement. Food and Agriculture Organization (FAO) recommends a minimum of 0.83 g/kg body weight of high-quality protein and 1,680 kcal/day for an adult. DDs may also induce stress, raise cortisol levels, and increase appetite, resulting in binge eating and weight gain.
As no convincing positive evidence exists for DDs and detox products, their use needs to be discouraged by health professionals. Moreover, regulatory review and adequate safety monitoring should be considered.
Turmeric is a commonly used herbal product implicated in causing liver injury. The aim of this case series was to describe the clinical, histologic, and human leukocyte antigen (HLA) associations of turmeric-associated liver injury enrolled in the U.S. Drug Induced Liver Injury Network (DILIN).
All adjudicated cases enrolled in DILIN between 2004-2022 in which turmeric was an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing.
Ten cases of turmeric-associated liver injury were found, all enrolled since 2011 and six since 2017. Of the 10 cases, 8 were women, 9 were White and the median age was 56 years (range, 35-71). Liver injury was hepatocellular in 9 patients and mixed in one. Liver biopsies in 4 patients showed acute hepatitis or mixed cholestatic-hepatitic injury with eosinophils. Five patients were hospitalized, and one patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products tested; 3 also contained piperine (black pepper). HLA typing demonstrated that 7 patients carried HLA-B*35:01, 2 of whom were homozygous, yielding an allele frequency of 0.450 compared to population controls of 0.056-0.069.
The authors concluded that liver injury due to turmeric appears to be increasing in the United States, perhaps reflecting usage patterns or increased combination with black pepper. Turmeric causes potentially severe liver injury that is typically hepatocellular, with a latency of 1 to 4 months and strong linkage to HLA-B*35:01.
Turmeric or curcumin is said to cause multiple effects, such as inhibiting inflammation, oxidative stress, tumor cell proliferation, cell death, and infection. Yet, sound clinical trials to test whether these effects might translate into health benefits are rare. In addition, the bioavailability of oral turmeric supplements is known to be low.
Turmeric has been used in food for millennia and is thus generally considered to be safe. Known adverse effects include gastrointestinal problems such as nausea and diarrhea and allergic reactions. Clearly, the new case series casts considerable doubt on the safety of turmeric. Yet, one ought to point out that the number of cases is low (but, on the other hand under-reporting can be assumed to be high). Furthermore, we should take into account that the quality of commercially available products is often low. One must therefore ask whether the liver injuries were truly caused by turmeric itself or by contaminants.
My conclusion is that turmeric is unquestionably an interesting plant with considerable potential as a medicine. At present, there is much hype surrounding it. Yet, hype is almost always contra-productive. If we want to know the true value of turmeric, we need to solve the bioavailability problem and do much more research into its safety and efficacy for defined conditions.
Yesterday, L’EXPRESS published an interview with me. It was introduced with these words (my translation):
Professor emeritus at the University of Exeter in the United Kingdom, Edzard Ernst is certainly the best connoisseur of unconventional healing practices. For 25 years, he has been sifting through the scientific evaluation of these so-called “alternative” medicines. With a single goal: to provide an objective view, based on solid evidence, of the reality of the benefits and risks of these therapies. While this former homeopathic doctor initially thought he was bringing them a certain legitimacy, he has become one of their most enlightened critics. It is notable as a result of his work that the British health system, the NHS, gave up covering homeopathy. Since then, he has never ceased to alert us to the abuses and lies associated with these practices. For L’Express, he looks back at the challenges of regulating this vast sector and deciphers the main concepts put forward by “wellness” professionals – holism, detox, prevention, strengthening the immune system, etc.
The interview itself is quite extraordinary, in my view. While UK, US, and German journalists usually are at pains to tone down my often outspoken answers, the French journalists (there were two doing the interview with me) did nothing of the sort. This starts with the title of the piece: “Homeopathy is implausible but energy healing takes the biscuit”.
The overall result is one of the most outspoken interviews of my entire career. Let me offer you a few examples (again my translation):
Why are you so critical of celebrities like Gwyneth Paltrow who promote these wellness methods?
Sadly, we have gone from evidence-based medicine to celebrity-based medicine. A celebrity without any medical background becomes infatuated with a certain method. They popularize this form of treatment, very often making money from it. The best example of this is Prince Charles, sorry Charles III, who spent forty years of his life promoting very strange things under the guise of defending alternative medicine. He even tried to market a “detox” tincture, based on artichoke and dandelion, which was quickly withdrawn from the market.
How to regulate this sector of wellness and alternative medicines? Today, anyone can present himself as a naturopath or yoga teacher…
Each country has its own regulation, or rather its own lack of regulation. In Germany, for instance, we have the “Heilpraktikter”. Anyone can get this paramedical status, you just have to pass an exam showing that you are not a danger to the public. You can retake this exam as often as you want. Even the dumbest will eventually pass. But these practitioners have an incredible amount of freedom, they even may give infusions and injections. So there is a two-tier health care system, with university-trained doctors and these practitioners.
In France, you have non-medical practitioners who are fighting for recognition. Osteopaths are a good example. They are not officially recognized as a health profession. Many schools have popped up to train them, promising a good income to their students, but today there are too many osteopaths compared to the demand of the patients (knowing that nobody really needs an osteopath to begin with…). Naturopaths are in the same situation.
In Great Britain, osteopaths and chiropractors are regulated by statute. There is even a Royal College dedicated to chiropractic. It’s a bit like having a Royal College for hairdressers! It’s stupid, but we have that. We also have professionals like naturopaths, acupuncturists, or herbalists who have an intermediate status. So it’s a very complex area, depending on the state. It is high time to have more uniform regulations in Europe.
But what would adequate regulation look like?
From my point of view, if you really regulate a profession like homeopaths, it means that these professionals may only practice according to the best scientific evidence available. Which, in practice, means that a homeopath cannot practice homeopathy. This is why these practitioners have a schizophrenic attitude toward regulation. On the one hand, they would like to be recognized to gain credibility. But on the other hand, they know very well that a real regulation would mean that they would have to close shop…
What about the side effects of these practices?
If you ask an alternative practitioner about the risks involved, he or she will take exception. The problem is that there is no system in alternative medicine to monitor side effects and risks. However, there have been cases where chiropractors or acupuncturists have killed people. These cases end up in court, but not in the medical literature. The acupuncturists have no problem saying that a hundred deaths due to acupuncture – a figure that can be found in the scientific literature – is negligible compared to the millions of treatments performed every day in this discipline. But this is only the tip of the iceberg. There are many cases that are not published and therefore not included in the data, because there is no real surveillance system for these disciplines.
Do you see a connection between the wellness sector and conspiracy theories? In the US, we saw that Qanon was thriving in the yoga sector, for example…
Several studies have confirmed these links: people who adhere to conspiracy theories also tend to turn to alternative medicine. If you think about it, alternative medicine is itself a conspiracy theory. It is the idea that conventional medicine, in the name of pharmaceutical interests, in particular, wants to suppress certain treatments, which can therefore only exist in an alternative world. But in reality, the pharmaceutical industry is only too eager to take advantage of this craze for alternative products and well-being. Similarly, universities, hospitals, and other health organizations are all too willing to open their doors to these disciplines, despite the lack of evidence of their effectiveness.
We have repeatedly discussed the issue of detox as used in so-called alternative medicine (SCAM) and seen that, for a whole range of reasons, it is utter nonsense, e.g.:
- Remember Prince Charles’ ‘Duchy Originals Detox Tincture’?
- Now that you have paid through your nose for the ‘tox’, how about a ‘detox’ through your nose?
- Homotoxicology: ‘the best kept detox secret’? No, it’s even worse than homeopathy!
- Detox is bunk; save your money for something useful, fun or pleasant!
- Scientology detox? No thanks!!!
- ‘DETOX’ = a dangerous and counter-productive illusion
- Have yourself a merry little detox
- It’s beginning to look a lot like DETOX…everywhere I go
But would it not be better to keep toxins from entering the body in the first place?
Yes, you suspected correctly: there are products that claim to do exactly this. Here is a particularly ‘impressive’ one:
ION* Gut Support seals cells in the gut lining, helping to keep toxins out of your body and strengthening the terrain upon which your microbiome can diversify. it uses Humic Extract (from Ancient Soil) and Purified Water.
Humic extract is sourced from ancient soil (roughly 60 million years old), and contains a blend of bacterial metabolites (aka, fulvate) as well as less than 1% of a variety of trace minerals and amino acids including chloride, sodium, lithium, calcium, phosphorus, sulfur, bromide, potassium, iron, antimony, zinc, copper, gold, magnesium, alanine, glycine, histidine, isoleucine, methionine, threonine, and valine.
… the trace minerals in our humic extract are naturally occurring, well below the RDI, and not meant to be used as supplementary to any deficiencies. The truly active compound in humic extract is the fulvate, a unique family of carbon molecules with oxygen-binding sites that are produced by bacteria when they digest nutrients. These molecules are the backbone of the ION* blend, helping with critical functions like cellular and microbial communication and chelation of nutrients.
The science behind ION* lies in strengthening the cellular integrity of your body’s barriers, including not just your gut, but your sinuses and skin as well. Keeping your cells connected keeps these barriers intact, which sets the stage (or “terrain” as we like to call it) for seamless interaction between you and your microbiome.
At ION*, we’re all about connection – starting with the very foundation of our science: tight junction integrity. Tight junctions are the seals between your cells which help to create defensive barriers at the gut, skin, and sinuses. They act intelligently to keep toxins and foreign particles out of the blood stream while also allowing nutrients to enter. These seals are protected by the carbon and mineral metabolites of bacterial digestion.
Unfortunately, tight junction barriers can be degraded with exposure to gluten, glyphosate (the main chemical in commercial herbicides like Roundup), and other environmental insults. ION* has been scientifically shown to promote the strengthening of this barrier through redox signaling, even in the face of those environmental insults.
Your body’s barriers know what to let in (nutrients) and what to ward off (toxins). But the barriers must be strong. ION* works to strengthen your gut, sinus, and skin barriers at a cellular level by fostering tight junction integrity, helping to promote this intelligent defense system at a foundational level.
So much scientific-sounding language can make your head spin.
Which toxins are we talking about?
Are there any clinical studies of the product?
Why is the product so expensive?
What exactly are Humic substances?
I found an answer to only the last question. Humic substances are organic compounds that are important components of humus, the major organic fraction of soil, peat, and coal, and also a constituent of many upland streams, dystrophic lakes, and ocean water.
I imagine that tightening the named junctions – if this is truly a realistic mechanism of action – might interfere with the absorption of all sorts of substances that the body needs for survival. I am, of course, speculating, but one should ask about the risks of using this product (other than the one to the consumer’s bank account).
What we need are clinical studies. And there seem to be none (if anyone knows one, please let me know).
So, what do we call again a health product that makes unsubstantiated claims?
Was it perhaps ‘snake oil’?
The present study was conducted to evaluate the effect of date palm on the sexual function of infertile couples. It was designed as a double-blind, placebo-controlled clinical trial conducted on infertile women and their husbands who referred to infertility clinics in Iran in 2019.
The intervention group was given a palm date capsule and the control group was given a placebo. Data were collected through female sexual function index and International Index of Erectile Function.
The total score of sexual function of females in the intervention group increased significantly from 21.06 ± 2.58 to 27.31 ± 2.59 (P < 0.0001). Also, other areas of sexual function in females (arousal, orgasm, lubrication, pain during intercourse, satisfaction) in the intervention group showed a significant increase compared to females in the control group, which was statistically significant (P < 0.0001).
All areas of male sexual function (erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction) significantly increased in the intervention group compared to the control group (P < 0.0001).
The authors concluded that the present study revealed that 1-month consumption of date palm has a positive impact on the sexual function of infertile couples.
In an attempt to explain the rational for this study, the authors state that, since ancient times, date palm has been used in Greece, China and Egypt to treat infertility and increase sexual desire and fertility in females. Rasekh indicated that Palm Pollen is effective in sperm parameters of infertile men. Administering date palm to male rats and measuring the sexual parameters of rats showed an improvement in their sexual function. Studies on animals have shown its effect on the parameters of semen analysis in male animals and increasing hormones.
So, the trial was what might call a ‘long shot’, even a very long one. But that does not render its findings less interesting. If the results could be confirmed, they would certainly have considerable significance.
But can they be confirmed?
I have some doubts.
Two things are remarkable, in my view.
- The study only had subjective endpoints.
- There was as good as no placebo effect in the control group.
How can this be?
One explanation might be that the verum and the placebo capsules were easily identified by their taste of other features. This would then lead to many patients being ‘deblinded’; in other words, the patients on verum would have known and expected to experience an effect, while the patients on placebo would have also known and be disappointed thus not even experiencing a placebo response.
This might be an apt reminder for trialists to include a check of the success of blinding in their list of outcome measures.
Dietary supplements are touted for cognitive protection, but supporting evidence is mixed. COSMOS-Mind tested whether daily administration of cocoa extract (containing 500 mg/day flavanols) versus placebo and a commercial multivitamin-mineral (MVM) versus placebo improved cognition in older women and men.
COSMOS-Mind, a large randomized two-by-two factorial 3-year trial, assessed cognition by telephone at baseline and annually. The primary outcome was a global cognition composite formed from mean standardized (z) scores (relative to baseline) from individual tests, including the Telephone Interview of Cognitive Status, Word List and Story Recall, Oral Trail-Making, Verbal Fluency, Number Span, and Digit Ordering. Using intention-to-treat, the primary endpoint was change in this composite with 3 years of cocoa extract use. The pre-specified secondary endpoint was change in the composite with 3 years of MVM supplementation. Treatment effects were also examined for executive function and memory composite scores, and in pre-specified subgroups at higher risk for cognitive decline.
A total of 2262 participants were enrolled (mean age = 73y; 60% women; 89% non-Hispanic White), and 92% completed the baseline and at least one annual assessment. Cocoa extract had no effect on global cognition (mean z-score = 0.03, 95% CI: -0.02 to 0.08; P = .28). Daily MVM supplementation, relative to placebo, resulted in a statistically significant benefit on global cognition (mean z = 0.07, 95% CI 0.02 to 0.12; P = .007), and this effect was most pronounced in participants with a history of cardiovascular disease (no history: 0.06, 95% CI 0.01 to 0.11; history: 0.14, 95% CI -0.02 to 0.31; interaction, nominal P = .01). Multivitamin-mineral benefits were also observed for memory and executive function. The cocoa extract by MVM group interaction was not significant for any of the cognitive composites.
The authors concluded that the Cocoa extract did not benefit cognition. However, COSMOS-Mind provides the first evidence from a large, long-term, pragmatic trial to support the potential efficacy of a MVM to improve cognition in older adults. Additional work is needed to confirm these findings in a more diverse cohort and to identify mechanisms to account for MVM effects.
This trial certainly has a few stunning features. For instance, its sample size was impressive and its follow-up period long. But it also has a few weak points. The study was conducted remotely via mail or telephone which means that compliance was impossible to control. Moreover, the outcome measures were subjective, and blinding was not checked. In addition, I fail to see a plausible mechanism of action. Most importantly, the generalizability of the results to the population at large seems questionable. It might make sense that older individuals many of whom might have low vitamin levels can profit from MVM. Whether this is also true for younger people who are well-nourished might be a different matter.
Developing interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is perhaps one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvement in individuals with subjective cognitive decline.
This randomized, double-masked, placebo-controlled phase 2b trial was aimed at determining the effect of longer-term spermidine supplementation on memory performance and biomarkers in this at-risk group. The study was a monocenter trial carried out at an academic clinical research center in Germany. Eligible individuals were aged 60 to 90 years with subjective cognitive decline who were recruited from health care facilities as well as through advertisements in the general population.
One hundred participants were randomly assigned (1:1 ratio) to 12 months of dietary supplementation with either a spermidine-rich dietary supplement extracted from wheat germ (0.9 mg spermidine/d) or placebo (microcrystalline cellulose). Eighty-nine participants (89%) successfully completed the trial. The primary outcome was change in memory performance from baseline to 12-month postintervention assessment (intention-to-treat analysis), operationalized by mnemonic discrimination performance assessed by the Mnemonic Similarity Task. Secondary outcomes included additional neuropsychological, behavioral, and physiological parameters. Safety was assessed in all participants and exploratory per-protocol, as well as subgroup, analyses were performed.
A total of 100 participants (51 in the spermidine group and 49 in the placebo group) were included in the analysis (mean [SD] age, 69  years; 49 female participants [49%]). Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P = .47) and secondary outcomes. Exploratory analyses indicated possible beneficial effects of the intervention on inflammation and verbal memory. Adverse events were balanced between groups.
The authors concluded that in this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage.
The absence of an effect might have, according to the authors, two reasons.
- The daily dose of 0.9 mg spermidine might not have been sufficient to achieve strong effects on memory function and biomarkers in cognitively healthy older individuals.
- The supplementation with dietary spermidine might not act as a memory booster, but rather prevent age-related memory impairment and development of AD, a possibility supported by evidence from animal studies.
I am tempted to add a third one: spermidine might not be effective at all for this indication (or any other condition)!