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Procera AVH® and Ceraplex
Procera AVH® is a widely-marketed "dietary supplement" promoted as a "memory pill." Allegedly, the non-prescription pill "may help your brain." How? It might sharpen your memory and mental powers; it might make "that slow-thinking, sluggish brain as sharp as a tack." Ceraplex is marketed as "a powerful brain detox formula...designed to help flush away environmental toxins from the brain to enhance memory and focus even further." In an advertisement that appeared in The Sacramento Bee on April 15, 2013, the first 500 people to order Procera are promised "a FREE supply" of Ceraplex. The reader is warned that "supplies are limited, so call now." Since everything on Earth is limited except our capacity for delusion, the makers of the claim are telling the truth, although it may not be the whole truth. The same claim about limited supplies of Ceraplex was made in a Procera AVH ad that appeared four years ago in the Bee.
I wrote about this product in 2009 in a newsletter. Harriet A. Hall, M.D., aka The SkepDoc, saw this same ad in her local newspaper last year and wrote a column about it on the Science-Based Medicine blog. Joe Cannon of Supplement-Geek.com also reviewed Procera. Their reviews are good examples of applying critical thinking skills to controversial claims about health benefits from supplements made in advertisements. (For examples of such products go to your local drugstore and take a look at the products on the shelves in the supplement section. For examples of such ads read the monthly Costco newsletter, which is usually chock-full of ads for various supplements aimed at those of us who are looking for a safe and effective way to get rid of our aches and pains and improve our declining mental powers.)
Many of these supplements follow a common marketing plan that should raise many red flags. Their ads look like newspaper stories. The copy is full of weasel words like "helps," "may," and "may help," and vague, non-scientific expressions with a positive-sounding vibe like "revitalizes" and "sharpens." The ads make vague references to scientific studies that have been published in peer-reviewed journals, but they rarely tell you where you can find these studies and, when they do, the studies always disappoint. They were based on small samples, weren't rigorously designed, didn't use proper controls (if they used any), had large dropout rates, were published in third-tier journals, or suffered some other fatal flaw. Testimonials from satisfied customers are a key selling point in the global alternative health marketing plan, but they are especially prominent in ads for supplements. You will never hear from the dissatisfied customers or see any evidence that a customer's improvement was based on more than just one thing following another and the word of a total stranger.
The authorities appealed to in ads for supplements are often described in inappropriate terms, such as "nominated for a Nobel prize." (There is no such nominating process that takes seriously the recommendations of private groups.) The language of the Procera ad has a strange reference to a "US Surgeon General Candidate" as saying this "memory pill helps the brain." What is a Surgeon General "candidate"? In the Bee ad this candidate is not named. Dr. Hall reports that in the version of the ad she saw the candidate was a Dr. Paul Nemiroff and that a Google search revealed that Nemiroff is "the inventor and seller of his own diet supplement product, Joint Formula 88." A Google search will also reveal that Nemiroff is a surgeon with an impressive curriculum vitae. Many readers may wonder: why hasn't my doctor told me about this wonderful pill?
The ads for these supplements usually provide a few items that a critical thinker should look for, e.g., authoritative figures with credentials like those of Dr. Nemiroff and the proper background testifying to the validity of the claims being made for the product. Unfortunately, most readers will not have any idea who these people are. The ad in my paper for Procera cites (with photo) a Robert Heller, M.D., and refers to the work of Dr. Con Stough at the Brain Sciences Institute. The bulk of the authoritative testimonials, however, comes from Joshua Reynolds, who is described as a "preeminent brain expert" and "lead formulator for Procera AVH." On the website for Brain Research Labs, Joshua Reynolds is featured as "the inventor of Procera AVH." The BRL website also features a photo of white-haired Gene Steiner, a pharmacist wearing his lab coat. Steiner also provides a testimonial in the Bee print ad. Just above Steiner's testimonial in the ad is a photo of something that looks vaguely like a hospital entrance with the caption noting that a scientific study had been "conducted at this university research facility" on "what may be the world's first truly effective memory pill." The facility is not named but at the end of the ad there is a disclaimer that "UCLA is not included in the product described in this material. The reference to Dr. Heller should not be taken as an endorsement by UCLA." There is no reference to UCLA anywhere else in the ad. Heller, by the way, is listed on the Brain Research Labs site as a co-creator of BRL with Reynolds and as "a board certified Internist and an Emeritus Clinical Professor of Medicine at UCLA Medical Center."
Before reporting on the Procera and Cerebrex supplements, there is one more item a critical thinker should consider before launching an investigation into the claims made in such ads as the one we are considering here: the disclaimer. In addition to the disclaimer about UCLA, there is another disclaimer in this ad that is common in the marketing of supplements: the quack Miranda warning.
This product is not intended to diagnose, treat, cure or prevent any disease. These statements have not been evaluated by the FDA.
The FDA defines drugs, in part, by their intended use. Drugs are "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease." The intent of Procera and Cerebrex is not to treat or mitigate any disease. No mention is made in the ad of dementia, Alzheimer's, depression, or any other disease. The pill is said to help memory, mental sharpness and focus, and mood. The pill "helps deliver oxygen and glucose to the brain" and "helps restore depleted neurotransmitters, which may help increase and enhance alertness, concentration, and memory" (emphasis added). But the pill is not advertised as something to take to treat a disease, so technically it's not a drug--at least it's not a drug according to the regulations that the FDA must follow. The pill is a compound of chemicals, one that can be derived from the periwinkle, one that occurs naturally in red meat, and one that is found in a type of firmoss. Even so, Reynolds and Heller do not claim that Procera is natural. They do note that it is not a drug. For many people, not being a drug is as good as being natural.
the big question
The one big question that all readers of such ads as the one for Procera and Cerebrex should ask is this: if this product is so wonderful, why isn't every doctor in the world recommending it to their patients? To their credit, Reynolds and Heller don't offer an explanation. Many other promoters of supplements make claims about conspiracies involving Big Pharma or the American Medical Association, but these fellows ignore the issue. We should wonder, though, why our doctors are so silent about such wonderful products. Are they unsafe? Do they have dangerous side effects that the inventors/sellers of the product aren't telling us about? Are the products too costly? Are they being overhyped? Is the research not really as good as the inventors/sellers claim?
looking for the truth beneath the hype
What is Procera AVH? According to Dr. Hall, Procera AVH contains acetyl-L-carnitine (ALC), vinpocetine, and Huperzine-A. According to the Bee ad, these are "three clinically validated brain boosting nutrients" that have been show to "light up aging brains like a Christmas tree." Where is this clinical validation?
From what I can gather at Google University, ALC mimics the neurotransmitter acetylcholine and for that reason has been the subject of several clinical trials on older people with memory problems. The latest publication on the issue that I could find is dated a decade ago. A review of 11 clinical trials concluded:
There is evidence for benefit of ALC on clinical global impression, but there was no evidence using objective assessments in any other area of outcome. Given the large number of comparisons made, the statistically significant result may be due to chance. At present there is no evidence to recommend its routine use in clinical practice... the evidence does not suggest that ALC is likely to prove an important therapeutic agent.
Vinpocetine has been widely marketed as a vasodilator and has been used in the treatment of vascular dementia, especially in eastern Europe. The latest study I could find on PubMed was done in Hungary and the translation (dated 2012) does not mention how many people were in the study. The authors recommend vinpocetine for "mild cognitive impairment." According to Dr. Hall, a Cochrane review found 3 studies of the effects of vinpocetine on adults with dementia. The results were inconclusive. One study was certainly too small to warrant any conclusions about the effectiveness of vinpocetine to help memory in healthy patients.
Huperzine-A, according to Joe Cannon, "inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine. As such, it will raise levels of acetylcholine in the brain. Because it can raise acetylchoiline levels, Huperzine A side effects may range from elevated blood pressure and muscle cramps to, vomiting, sweating, seizures and blurry vision." Dr. Hall found that a "small study of students in China showed improved memory and higher test scores. Some studies in adults with dementia were favorable, but a Cochrane review found inadequate evidence to draw any conclusions."
The independent reviews done by Dr. Hall and Mr. Cannon return quite different results from the rosy picture painted by Heller and Reynolds, the founders of Brain Research Labs. Oddly, none of the published studies on the components of Procera AVH came from their lab. Even more odd is that Cannon located Brain Research Labs in a residential area of Murfreesboro, Tennessee. I checked NetWorkSolutions and found that the website for Brain Research Labs is registered to KeyView Labs, Inc., 1680 Fruitville Road Sarasota, Florida 34236. A Google map search shows that there is a law firm building at that address, not a laboratory. A news article dated January 16, 2013, reports that some investors put $11.4 million into KeyView Labs Inc., a consumer health products firm based in Sarasota. It used the funding to buy Brain Research Labs. Business Week describes KeyView Labs as "an online retailer of consumer health products for brain health, longevity, and cognitive performance." In other words, neither Brain Research Labs nor KeyView Labs is a lab.
So, where was the laboratory research done that is touted in the Procera advertisement? Both in their print ad and on their website, the Procera promoters rely on one man in one lab to do the heavy lifting: Dr. Con Stough at the Brain Sciences Institute, Swinburne University, Melbourne, Australia. The website for the Brain Sciences Institute does not list Dr. Stough as being on the research staff. However, he is listed as a Professorial Fellow of Swinburne University. He has an impressive list of publications, only one of which is relevant to Procera AVH: "A randomized, double-blind, placebo controlled study examining the effects of a combination nutraceutical formula on cognitive functioning and mood." JANA, 12, 12-19. I'd never heard of JANA until reading the ad for Procera, which refers to it as "a leading peer-reviewed scientific journal." Dr. Hall discovered that JANA is the Journal of the American Nutraceutical Association, "an obscure journal that was published erratically (1-4 issues a year) from 1996 to 2009. It’s not even listed in PubMed. The article is available online for free.
The grand validator study by Stough et al. was short (30 days) and small: 43 in the combination nutraceutical formula group and 31 in the control group. The study started with 45 subjects in each group, so the dropout rate was much greater in the control group (31% vs. 4% in the experimental group), which could be due to a fluke or to some tell that the participants picked up on. The average age was 49.5 years in the experimental group and 47.1 years in the placebo group. "The dose was 1,515 mg per day and each participant was instructed to take 3 pills per day. The combination nutraceutical formula, known as ProceraAVH, was provided by 20/20 Brain Power Partners, LLC (Founders of Brain Research Labs), Laguna Beach, California. Half of the research funding also came from the providers of the product.
The researchers assessed "a range of cognitive functions, including attention, information processing, sub-loops of working memory, reasoning, secondary memory, and skilled coordination." The study found "non-significant changes in simple reaction time, digit vigilance and choice reaction time, spatial working memory and picture recognition, (long term memory consolidation of objects)." As would be expected in any study that measures dozens of variables, a few changes were significant, such as numeric working memory and speed of performance during the word recognition task. There were also several differences between the two groups that did not rise to the p<.05 level, which is also to be expected when a large number of factors are measured and compared. Overall, the best I can say about the study is that it was well-designed, used a number of reasonable screening techniques, and didn't go overboard in recommending Procera AVH as the new wonder drug. Before drawing any conclusions about the benefits of Procera AVH, I would have to see more studies done with larger numbers of participants over longer periods of time. I would also like to see some justification for how the makers of Procera came to the formula of 1,515 mg for each pill to be taken 3 times a day. (Cannon was told by someone at Procera customer service that the pills contain equal amounts of each of the three ingredients.)
Do you need to detoxify your brain?
There isn't much scientific support for Procera AVH, it seems. But what about Cereplex? According to BRL, Cereplex is "a natural, multi-action brain anti-oxidant, detoxification, and neuro-protective formula designed to help protect your brain against the daily onslaught of a broad spectrum of 'toxins' and stressors - including free radicals, stress hormones and aging." What research has the "lab" done on this one? When Joe Cannon investigated Cereplex, the address for BRL had changed to one in Spokane, Washington. This "lab" is also in a residential neighborhood.
Cereplex has six ingredients, each of which is an anti-oxidant or an anti-inflammatory. As far as I can tell, there's been no study of Cereplex similar to the Dr. Stough et al. study of Procera AVH. The thinking of the inventors of this product might be that since there is some evidence that these ingredients alone and separate might help some people in some ways, then a compound of the six together might help some people's brains. Maybe. Maybe not.
Is there strong scientific evidence that the quantity of toxins most of us have in our brains is causing significant cognitive loss? I'd like to see the evidence, if it exists. According to the BRL website:
Thousands of clinical studies over the past 20 years have shown the ingredients in Ceraplex to be effective in reducing free radicals (oxidative stress), inflammatory markers (e.g., cytokines, COX-2 & 5-LOX), and neurotoxic by-products of cellular respiration and oxidation (i.e., metabolic debris), especially in the mitochondria.
The claims for the ingredients of Cereplex may be true, but that doesn't tell us that they'll work well together or give us any idea of what dose, if any, would be appropriate. Here we have the research on other products done at other labs being put forth as scientific evidence that an untested product is safe, effective, and validated. At this point I'd consider any money spent on Procera or Cereplex wasted. Unfortunately, I don't know where to lodge my concerns, but I've whittled down my list to somewhere in Tennessee, Washington, California, or Florida.
Finally, readers should consider what the promoters of Procera and Cereplex say the buyer of brain supplements should be aware of:
Was the clinical study conducted on the product per se, or does the marketer of the product merely cite clinical studies on the ingredients in their product?
If so, does the product actually incorporate at least the minimal dosage level that a consensus of qualified clinical studies prove efficacious.
Did the study test a significant sample size, e.g. 75-100 subjects....
Finally, was the study conducted in healthy, cognitively normal individuals representing a broad age group of male and females or in cognitively impaired individuals?
The answer to each of these questions is 'no' for Cereplex. Procera itself was studied by Stough et al. No evidence of how dosage was arrived at is provided. The study started with 90 healthy individuals, but about one-third of the control group dropped out. The study was conducted on a broad age-group of healthy individuals, but the product's marketing plan seems to be aiming at people who self-diagnose as having memory and other cognitive problems. I'm sure that someday there will be a pill to replace physical exercise, but for now it seems that the best way to take care of your brain is to avoid the usual suspects (alcohol, methamphetamines, etc.) and take a vigorous walk or do some aerobics.
Evaluating Personal Experience by R. T. Carroll
review of The Invisible Gorilla: And Other Ways Our Intuitions Deceive Us by Christopher Chabris and Daniel Simons
Last updated 18-Nov-2013