The Good, The Vague and the Disservice
Communicating Natural Product Science with Consumers
Introduction
Exchanging new scientific information, breakthroughs and guidelines with the general public is challenging. One wants to be engaging, maintain an educational focus and potentially, help define courses of action and areas to avoid. The goal is to provide the consumer with the tools to make informed decisions and generating optimal health and wellness.
That is a tall order. Not easy but there is an onus that the information be accurate, easy to comprehend and apply. Fortunately, there are numerous tools available to ensure a successful educational outcome e.g., videos, powerpoints, webinars, zooms, shared scientific publications, lay orientated summaries and position papers, as well as a plethora of social media outlets. That is a powerful array of options. By comparison, when one approaches their physician for advice and guidance the options are quite paltry and often parroted information from a pharmaceutical company.
Within the Natural Products Industry there are some excellent examples of where science has been well communicated, forming meaningful connections with the consumer that are rewarding and sustained. Nevertheless, there are numerous examples of where the information exchange is less than optimal, bordering on misleading or at least factually inaccurate.
What is behind this gap?
There are several primary reasons. Firstly, the training, experience and education of the “experts” discussing the science may be limited. This can apply no matter their background, degrees and position. Often, there are major gaps in their understanding of how the body works and drivers behind dysfunction. However, it is incredibly hard for consumers to determine what information is accurate, fuzzy, without merit or plain sloppy.
Often over-simplification is a core element for the confusion. At other times, marketing groups do not spend adequate time explaining the science behind a product or approach. Rather they get wrapped up in the story they want to exchange glossing over whether it is valid, supported or accurate. There are numerous examples of where scientists, physicians and other healthcare providers fail to remain engaged with a bigger picture, or they may remain embedded in dogmas and agendas thereby limiting the potential benefits. Then there are numerous examples of groups whose sole intent are to gain short term revenue, with disregard for consumer outcomes. Less sinister but more common, there communication programs chasing hot button fads, in vogue words and scientific terms albeit delivered in a clumsy, inaccurate manner.
In this article I want to draw attention to the times where excellence has shone through and to deliver the appropriate accolades. At the same time, I want to generate conversation as to when the system is not working well or in the best interest of consumers. My hopes are that with dialogue we can improve overall education and training leading to better health outcomes.
NOTE: I have held positions in science (Medical School Professorships, CSO), Drug Discovery (Pharmaceutical Research Fellow), Marketing (VP), Manufacturing (CIO) and Strategic Business Development (Private Equity), so my perspective is broad, emanating from decades in the trenches. The intent is to be proactive, but all players will be held to account.
The GOOD
One group that richly deserves accolades are ingredient companies that go out of their way to validate and define their product with clinical trials. They are commendable source of innovation. This pursuit of excellence helps set expectations as to onset of benefits, magnitude of the outcomes, specific delivery systems. This was rare 15 years ago but now there is a trend for using science to define the value of an ingredient, and then use that data for marketing purposes. These efforts deserve acknowledgment and sincere gratitude. Scientific studies helps elevates the conversation to a fact-based exchange rather than a series of passionate but albeit vague opinions, where all advice has equal weight.
I hope that this trend of investing in clinical research and preclinical mechanisms of action studies continues. Just to highlight how far this can go, AstaRealÒ, which makes a single ingredient, astaxanthin, has performed at least 70 clinical trials and a total of over 145 scientific studies on its one ingredient. Why? Because astaxanthin has massive health benefits but is largely unknown to consumers because it is not accessible in adequate amounts in the diet. Hence, it is largely peripheral to the diet-health conversation. AstaRealÒ overcame this massive gap and created an entire market around its amazing compendium of published scientific studies. Accolades.
We need good science to guide us. Better information leads to better decisions and superior outcomes.
An obvious way to reinforce the value in this approach is to construct products with ingredients that have clinical or pre-clinical support and then effectively communicate the actions and value of those ingredients.
However, not all clinical trials work as expected. That is the inherent nature of research. When outcomes drift from what was expected and fail to yield the desired claims and positioning there is a temptation to use statistical hijinks in a salvage operation. Therein lies the dilemma as health care providers often may refer to the catchy headline and iterate the myth without reading the study in detail, or dive into the statistics to assess its validity.
Having been a reviewer, editor or editorial board member of over 65 biomedical journals I have seen a lot, the good and the ugly. I remain concerned that there is trend that bad science, or invalid conclusions are published and disseminated with manipulation. Previously, these substandard reports would simply be rejected by the journal (journal acceptance rates were historically quite low e.g., 30%). Now, spurred by the massive growth of the number of journals that are hungry for papers, the quality has declined. Hence, scientific publications may or may not be supportive of the conclusions. Care is advised and when evaluating any supportive science it is important to go beyond the headlines and abstract.
Let’s talk about examples of where the messaging has been clear, well supported and appropriate.
Bioavailability
Historically this is a pharmacological term used to quantify the absorption of a biochemical (drug). This is of vital importance when a nutrient is poorly absorbed, resulting in its loss through the feces. There are numerous reasons why this poor absorption takes place but remember the epithelial lining of the gut has a very discerning role. It must be able to identify valued biochemicals and actively grab them and absorb them, sending then to the liver, via the blood, for collation, distribution, modification or storage. The epithelium must also function as a barrier for unwanted components, toxins, contaminants, pathogenic bacteria, yeasts, viruses and parasites.
When this nutrient absorption process is limited, its value is substantially reduced. Science has developed ways to overcome this hurdle. The concept is essentially based on the legendary Trojan Horse, where Greeks entered the city of Troy from within a wooden horse structure, unbeknownst to the Trojans. Once inside the City of Troy, the Greeks emerged. In gastrointestinal physiology we have converted that concept by using carriers for poorly absorbed but highly valued nutrients. The nutrient is embedded with a sphere of material that the gut epithelium recognizes as being of value, leading to an active effort to absorb it.
Some of the best examples of how to use phytosomes and liposomes (in this analogy they are the Trojan Horse) to improve the delivery of curcuminoids into the circulation for systemic actions. Curcuminoids have an excellent profile of benefits, often linked to anti-inflammatory roles, modified cellular decision making and brain health, but they are notoriously poorly absorbed. For this reason, the parent botanical, turmeric, has limitations based on poor bioavailability.
Therein lies the challenge. Here we have a valued bioactive that we struggle to get absorbed but can truly have a significant impact on health and wellness. Solutions like liposomes and phytosomes that are recognized as being valuable by the gut epithelium and actively absorbed, enable for a marked increase in curcuminoid absorption and disposition.
Bioavailability is a technical tool that science has provided a solution for the unmet consumer need and to define value of one option over another. Further, consumers can understand it. They can use it to differentiate a superior product over the mundane or ineffective. Information that leads to better health outcomes. I see this trend continuing.
Microbiome
The science of the microbiome has been advancing at an enormous rate and inroads into consumer thinking has been successful. The challenge was not insignificant as when discussing bacteria, the public has been told over decades that all bacteria are germs, and the cause of infection, illness and are to be avoided. When discussing the two other critical elements of a healthy microbiome, fungi and bacteriophages, the educational battle gets even harder.
Initially, we crossed this bridge by drawing upon traditional foods. For example, yogurt is traditionally made with three bacteria generating lactic acid and lowering the pH of the food, and that led to the ability to class them as “good bacteria” as opposed to germs. Similarly, sourdough bread captures the airborne yeast Saccharomyces boulardii facilitating the biotransformation of the dough to bread. Another related yeast S. cerevisiae is important in brewing, which historically was an invaluable way to generate safe fluids when water supplies were contaminated and refrigeration unavailable, whilst delivering at the same time B vitamins and products of the yeasts metabolism (which we now call post-biotics).
Linking new scientific breakthroughs to familiar traditions, especially dietary, has proven to be very successful in educating and engaging with consumers.
Likewise fermented foods that have “good microbes” like Kimchi and sauerkraut, helps embed scientific concepts into the minds of consumers. Leaping from this base has come an avalanche of scientific research on probiotics. Whilst initially communications and applications were focused on gastrointestinal issues, it has expanded into a multitude of systemic actions – obesity, metabolism, brain, sports performance and skin health.
Given the complexity of the microbiome there remains a lot of work to do on consumer education. A healthy microbiome, balanced and resilient, has now been shown to have impacts on our health far beyond the gut. Given that the microbiome brings 10x more DNA (genes) to the community than our own genes, it is easy to see the impact. In essence our being is one of a dynamic, changing community. However, we face challenges when describing how the microbiome can be a driver for obesity, depression and mood, cardiovascular health, sports performance and skin health to name just a few. The science is there but regulatory bodies are uncertain as to how what can be said. For example the European Food Safety Authority (EFSA) still refuses to associate structure-function claims to probiotics, based on an uncertain mechanism of action.
While microbiome science is advancing rapidly, with thousands of supportive studies and publications, the excuse of needing to know more before allowing claims, seems very tepid and limits the much needed conversation we should be having with consumers.
Nevertheless, the task will be lightened with continued scientific progress drawing attention to the opportunities to maintain or regain health and wellness. Social media touting these research results certainly helps, but it must be done correctly as misinformation can turn the populace away from innovations before they can become mainstream.
Brain Health and Cognition
The pharmaceutical companies have invested substantial efforts to create blockbuster drugs for dementia; efforts that have been largely disappointing. Embedded in that failure was the concept that tau protein tangles and Beta-amyloid plaques were the drivers of neuronal death, changes in brain form and the decline in cognitive function. As it turns out plaques and tangled proteins are the result of numerous upstream events, often linked to inflammation and its associated oxidative stress and the burden of reactive nitrogen species. They are more correctly classified as consequences of dementia rather than the cause. Failing to understand the core, critical drivers of a compromised health state, rather than its sequelae, limits the effectiveness of any approach to health and wellness. There are numerous effective natural products that address these critical upstream events, although it is problematic discussing these events as it relates to dementia.
Depression and mood have been a successful target for pharmaceutical approaches centered on manipulating various neurotransmitters. Nevertheless, the significant side-effects of these drugs have driven consumers to seek kinder and gentler alternatives. Into that unmet consumer need steps in Natural Products Industry, and they have done a good job. Given the diversity of the human condition and the various factors that impact brain health, the industry has performed well with diverse offerings.
Solid research supports the benefits to a wide range of natural products. They include the unexpected (probiotics) to replenishing neurotransmitters with precursor biochemicals. It has also learned from traditional medicine especially botanicals e.g., using L-theanine from tea, the carotenoids astaxanthin from algae and lutein from leafy greens, kava from Melanesia, curcumin from Ayuvedic medicine, and saffron from Middle Eastern cultures.
There are a plethora of well supported natural product offerings to enhance decision making, reduce errors, improving memory, to producing a state of calmness in the face of anxiety. Accolades.
Sleep and Stress
Stress, anxiety and poor sleep became hot ticket items with the global pandemic. Here again the Natural Products Industry provided much needed options. The approach can be quite varied. Adaptogens have become very popular, to the point there are concerns that limited botanical resources may be overwhelmed by consumer need. Rhodiola rosea is a prime example, and accolades to the ingredient companies that value their supply chain with innovative, sustainable farming techniques. Nevertheless, the messaging of how adaptogens mediate their actions, e.g., heat shock proteins, remains clumsy and at times consumers remain confused.
Magnesium for sleep has become very popular, oddly at times as there was a groundswell some years back when it as regarded as a problem by some. I think consumer experience and word of mouth overcame the unsupported concerns.
Various botanicals other than adaptogens, have become popular. Saffron, well known as a valuable cooking component, rose in popularity because of a series of excellent scientific studies. I will table CBD and related cannabinoids like Delta-8 THC and Delta-9 THC, as their messaging is still a conglomerate of politics and regulatory concerns.
The VAGUE
IARC & WHO and Aspartame
Recently mass confusion arose over the non-nutritive sweetener, aspartame. The IARC and WHO classified aspartame as possibly carcinogenic. For those who are unfamiliar, the WHO takes its cancer guidance from a group called the IARC. Essentially the WHO rubber stamps the IARC recommendation. In the case of aspartame, the IARC could not define a clear concern so they threw it into their catch-all classification of possibly may be carcinogenic in humans, placing it in category 2B Aspartame, Cancer and IARC/WHO The IARC (WHO) has no clear evidence that it will cause cancer, so to be conservative they throw it into this poorly worded, vague classification. Not helpful in terms of advising consumers, but not the first time the IARC has issued misguided edicts based on sloppiness and self-adulatory conservativeness.
The media frenzy arose because the title is too vague and it created a slew of headlines that it took it too far, claiming that it was indeed, carcinogenic. When combined with an agenda for disliking non-nutritive sweeteners, per se, the media ran with edgy headlines that perpetuated a myth. The bottom line is that all regulatory agencies view aspartame as being safe. Further, as a dipeptide (two amino acids), it can be found naturally in many proteins. Indeed, it was discovered as the last two amino acids of a hormone that regulates gastric acid production from a research team trying to develop innovative solutions for ulcers. Knowing the source, one gains additional perspective that helps define the IARC/WHO action as being inept.
When Diet is not Enough – Food vs Supplements
A common refrain from dietitians is that unless the nutrient comes in food then it is not valuable. This comes from their training, which is diet-centered and focused on overcoming poor health when it is driven by states of deficiency. When used for this purpose there is indeed value when educating consumers.
One of the classic components at the core of therapeutics is DOSE. Food is often the source of incredible value, but it is not uncommon that the amounts of a valued natural product in food is too low for it to be effective. Trying to raise the delivered dose by eating more food is not the answer, but supplementation of the diet does address the issue. One must also account for all the other elements in food, some are important, and some are not needed. Concentrating the desirable natural product whilst eliminating unnecessary components in the parent dietary source, via supplements, allows one to target specific problems with the therapeutic amounts and in safe manner.
This concept of natural products as therapeutics is central to why dietary supplements are regulated differently from food and from drugs. When done correctly, they provide valuable health solutions, help maintain wellness and obviate concerns about the poor quality of food, based on excessive storage, transportation and collection before the food has reached an optimal value (ripening). The edict that all natural products must come from food and not supplements is an inherently flawed proposition. Indeed, tabling efficacy for the moment, it is clear that food per se, is eminently more dangerous that dietary supplements Lunch is Killing Me
Nitric Oxide
The biochemistry of nitric oxide (NO), how it is generated and its roles in health and disease, is a classic area where the science has existed for several decades but is routinely misconstrued within the natural products industry. Why? Because the messaging is easier when one focuses on a simpler story. Having been a pioneer in this field of science I am sensitive to the misinformation that exists and repeated ad nauseum.
Nitric Oxide is a free radical (often ignored as we are taught to be scared of free radicals) generated from an amino acid, L-arginine, by three different enzymes (nitric oxide synthases, NOS). Additionally, NO can be regenerated in small amounts from the oxidative end-products, nitrite and nitrate, but this role is over-hyped. The natural products industry focuses almost entirely on the endothelial form of (eNOS) as the vascular production of NO is deficient in cardiovascular disease. On a personal level this is heartwarming that so much discussion and product applications involve correcting this deficit, because when I made the pioneering discovery in the 80’s of this endothelium-dependent pathology, I knew at the time of my discovery that it was a big deal Endothelium Dysfunction & HYpertension Some 9 months later, two independent groups (Bob Furchgott and Lou ignarro) found that the vasorelaxant mediator generated by the endothelium was indeed nitric oxide. For this critical discovery they received the Nobel Prize Nitric Oxide and The Nobel Prize. Nearly 40 years later and the science holds true, as does its critical role in vascular health.
What is disappointing are several other vital discoveries made around nitric oxide in this era are neglected by the natural products industry. Firstly, there is the total disregard as to the role of the immune and inflammation related isoform of NOS, called iNOS. This isoform is normally dormant and is only activated on demand. A critical feature of iNOS is that it consumes all the L-arginine it can get, for this reason L-arginine is classed as a semi-essential amino acid. In states of immune activation dietary arginine is essential, because iNOS consumes it on a massive scale. The other isoforms (eNOS and nNOS) only make NO from arginine on a small scale (puffs) albeit constantly.
With iNOS activation large amounts of NO are produced, the purpose of which is to kill cancer cells and invading infections. The downside is that this barrage or reactive nitrogen species is somewhat indiscriminate. My discovery that iNOS generated NO is a powerful driver of inflammation and tissue damage creates a role reversal that is totally ignored by the Natural Products community, largely because it is inconvenient. It detracts from the marketing message. Further the damaging effects of iNOS-induced NO formation results largely from its conversion to other reactive nitrogen species, in an analogous manner to how oxygen gives birth to reactive oxygen species. A case of good parents having bad children (biochemically speaking).
Another one of my discoveries on reactive nitrogen species has significant implications on nerve and mitochondrial health. We noted that because NO and O2 are both more soluble in lipids than water, as a result they react at a rate that is accelerated 270x in lipids. Why is this important? It is critical because the reaction yields the gases that make up SMOG, i.e., NO2 and N2O3. Literally the brown gases in smog. These possess quite damaging effects on membranes and beyond.
The dilemma is that when L-arginine supplements is advocated in conditions where iNOS is expressed, you are essentially feeding a machine that promotes damage and dysfunction. Nitric oxide here is pro-inflammatory and not the anti-inflammatory role evident with either nNOS or eNOS. Therapeutically, benefits arise from suppressing NO production rather than enhancing it. My discoveries in this area of nitric oxide are not recent, indeed they at least 30 years old, with the concepts entrenched in our scientific knowledge base through repeated replication. More details as to this enigmatic role reversal are contained in a previous Substack article Enigma of Nitric Oxide
The failure of the industry to account for these variances in nitric oxide chemistry remains worrisome. Consumers remain largely unaware of these consequences. Clear communication and discussion would result in superior, focused applications.
Inflammation (Acute vs. Chronic)
Communicating the dynamics of inflammation with consumers is another example of substantial confusion. This is because the media and the industry openly discuss inflammation in one catch all term. It fails to distinguish ACUTE vs CHRONIC, a misleading simplification as they are regulated entirely differently, with different mediators and respond to different therapeutic tools.
Simply put, ACUTE Inflammation is of a shorter duration and CHRONIC is long lasting. An example of effective agents for the symptoms of acute inflammation is aspirin or the related NSAIDS like ibuprofen and naproxen. By contrast an example of a therapeutic agent for chronic inflammation are the glucocorticoids, like prednisone.
Acute inflammation is inherently self-resolving, but we seek aids in managing the symptoms e.g., pain, redness, swelling, temperature elevation and some loss of function. All the things that bother us. Whereas chronic inflammation can share some of those characteristics, e.g., in arthritis symptoms can overlap, and NSAIDs can offer some symptomatic relief. This is because of the Venn Diagram of inflammation arthritis overlaps between acute and chronic inflammation. What is vital to know is that therapies directed at the symptoms of acute inflammation (NSAIDs) have no impact whatsoever on the disease progression. While they may provide short term benefits on pain management and swelling, the slow degradation of cartilage health continues unabated until we are left with a bone-on-bone scenario because NSAIDs do not abrogate chronic inflammation.
Similarly, atherosclerosis or hardening of the arteries is an example of chronic inflammation but devoid of symptoms that one associates with acute inflammation. Vascular disease continues unabated and is not sensitive to classic therapies used in acute inflammation. On a positive note interventions with natural products like Vitamin K2 is an incredibly useful tool. Vitamin K2 draws calcium out of arteries and redirects it to bone (where we want it). However, there is much work to be done in communicating these benefits. For example, on my recent annual physical I discussed this with my physician, and he had never heard of Vitamin K2 or this action. Again, the point is effectively communicating new, innovative science is important across the spectrum of those involved in health maintenance.
Related to vascular disease, there are certain natural products that are effective free radical scavengers and who degrade lipid peroxides. Suppressing the transport of rancid lipids from the blood into the blood vessel wall essentially arrests the atherosclerotic process. Astaxanthin, a natural carotenoid (strictly a xanthophyll) has been shown to suppress the transport of rancid lipids by lipoproteins, but it also activates a gene in macrophages within arteries, to toss cholesterol out of the blood vessel and back into the circulation. Serious benefits.
When the actions of natural products are more effectively discussed, using a platform of science, then we can approach health and wellness in a more meaningful manner.
Free Radical Scavengers and Antioxidants
Another case of simplification leading to confusion is the area of “antioxidants and free radical scavengers”. The terms are used interchangeably, which is not an accurate reflection of the chemistry.
To clarify, a free radical is simply a molecule that has an unpaired electron in its outer orbit. Molecules hate that. They desperately want their electrons to be paired up like dancing partners. This is why they are reactive. They will either donate the electron to another molecule or grab one to pair with the one they have. Molecules do not like their electrons dancing by themselves, so partnerships are sought. In chemical terms this could be an oxidative or reductive process. If it is a reduction process, then antioxidants do not “work”.
Further, molecules that receive an electron may themselves become a free radical – if the outer orbit is not paired. There are many examples where antioxidant molecules can act as a pro-oxidant. Vitamin C is an excellent molecule. That creates an enigma that is often overlooked. Transition metals are excellent as free radical scavengers because they can flip their redox state. For example, iron (Fe) can exist in ferrous (Fe2+) and ferric forms (Fe3+) as they can flip between those redox states by donating or receiving an electron. That is the basis for ability of superoxide dismutase (with its transition metals copper and zinc) converting the free radical superoxide (O2-) into H2O2 (hydrogen peroxide). This is a critical defense against the free radical superoxide that is generated from oxygen in mitochondria as they generate ATP. For the sake of clarity, hydrogen peroxide is an oxidant but not a free radical, whereas superoxide is both.
When a free radical hits a lipid target it turns the lipid rancid, technically it is called a lipid peroxide. That lipid peroxide will zip from one lipid to another in a propagation reaction that can only be stopped by a free radical scavenger. Astaxanthin is a great example of a natural product that negates lipid peroxides and is pure in that action, as it pairs up the electron (getting a dancing partner for it) whilst not succumbing to being a free radical itself.
All in all, while there is a need to explain these events clearly, as that defines how one can abrogate the damage. Using the terms free radical and oxidant interchangeably is both inaccurate and problematic. I understand that the chemistry can be a challenge, but just ignoring the implications will not yield better products nor targeted applications.
Patents
When a natural product is patented, it carries an aura of value and superiority. Indeed, that could very well be the case, patents are used to protect the competitive edge in the market for an ingredient or formulation, by blocking out the competition. However, be aware that often natural products are often patented for applications that are far from the intended use. Here obfuscation is the intended purpose. Hence, use caution when expecting to license a patent for a specific application as it may not provide you with the exclusivity that your expect.
Collagen Protein/Peptides/Amino Acids/Vegan
One of my pet peeves in the Natural Products industry is how we have discussed collagen, the protein, and products that are promoted as being able to increase your collagen levels. I discussed this at length in another Substack article Why Collagen Supplements are Like IKEA furniture .
This market is a minefield of misinformation and obfuscation whose sole purpose is to create an illusion of benefits. Very few do it correctly.
Firstly, there are no collagen supplements per se. Why? Because the protein is not what is being sold. Collagens are gnarly and tough and not conducive to formulating in a liquid, a capsule or powder. What is commercialized are collagen peptides not protein. Remember, the rank order of size is protein>peptide>amino acids. The commercial products are peptides i.e., fragments of proteins, created by acid and enzyme hydrolysis. The digestive process breaks down proteins into peptides and then in turn, the gut digests them further to amino acids which are the forms that are absorbed. There are some examples of small peptides (2 or 3 amino acids long) that are absorbed, but the gut lining does not normally allow peptides to cross the barrier as it creates allergic reactions.
There are some solid companies that sort through this soup of peptides, generated from pre-digested collagens, and from this soup only select ones that have been found to activate fibroblasts to create collagen locally. Importantly, these small peptides must be absorbed intact for them to be bioactive. These collagen peptide products are often backed by clinical trials supporting this action. Companies that follow this approach are to be applauded.
Usually however, consumers are led down a rabbit hole that discusses the amount of protein (peptides), the animal source or even the ludicrous notion of vegan collagen. Despite the fact that only animals have collagen, vegans want in on the action, and so genetically engineered fermenters (bacteria or yeasts) are used to create peptide sequences that are found in collagen. But note, these are just peptides and upon ingestion they are broken down to amino acids by the digestive system. The question arises that if an amino acid sequence is derived from an animal protein (again collagens are animal proteins) can it truly be called vegan? Are vegans happy that the product is from genetically engineering microbes? Finally, it is not a protein, it is a slew or peptides and amino acids. It is easy to see where people can be confused, but marketing takes advantage of that confusion by blurring the science.
Altogether this misuse of terms makes vegan collagen a poster child for vague nomenclature that is designed to tap into emotional strings in the market, rather than deliver value, educate and solve problems.
Assumptions Abound in the Collagen Market
Poor explanation of how the body maintains a healthy matrix, including its collagen networks are prevalent. In part because the entire market was created to sell what was previously waste proteins – rooster combs, fish scales and skin, bovine skin and hoofs, porcine trachea etc. Companies wanted to commercialize these waste proteins and so a marketing message was needed to create the consumer demand, when previously there was none.
Within the pitch and knowing that consumer appreciation of gastroenterology and matrix health, a slew of assumptions were made as the market was created. Here are some of them:
· Collagen supplements contain collagen – Actually they are collagen peptides and amino acids not the protein.
· They are absorbed and delivered to the locations that you want and then reassembled as collagen – Amino acids and some small peptides in the circulation hit all tissues in the body, as such targeted production of collagen seems less likely than overall production if it was solely dependent on the presence of amino acids.
· Merely ingesting collagen fragments leads to more collagen – the issue here is that like all reactions in the body, collagen formation is controlled by processes (enzymes etc.) not by the substrate that is being used. If the enzymes that generate collagens are not active (they can be rendered dormant during oxidative stress, UV light and inflammation) then merely ingesting substrate will not have any effect. If the generation of collagens was only dictated by substrate presence then they would be produced everywhere in uncontrolled amounts leading to general tissue fibrosis and scarring. Fibrosis and scar tissue formation is never discussed even though they are examples of collagen formation.
· I prefer one animal source over another – A common debate that defies how the body works. As long as the enzymes that create the collagen is present and active, they will string the amino acids in the correct sequence. It matters not where the amino acids came from, as one is not recreating fish skin, or hooves etc. the collagen forming enzymes are simply using those individual amino acids, like pearls, to recreate the pearl necklace that would be an intact collagen protein.
· Do not discuss matrix breakdown – As much as we like to discuss the need to generate more collagens, especially with age, there is negligible discussion on the impact of enzymes that degrade collagens, known as MMPs (matrix metalloproteineases). These are activated by UV light, inflammation and function to chop up collagen. They are regulated by gene switches that also control the enzymes that make collagen. When MMPs are activated, i.e., during oxidative stress, the enzymes that make collagen are turned off (rendered dormant at the gene level). You cannot solve deficits in collagen by ignoring MMPs, whose activity is totally independent of amino acids ingested by collagen supplements.
· I need a specific form of collagen e.g., Type 2 – There are 28 different collagens (each with their own gene/enzyme) and while some tissues have certain forms as the dominant, they are never singular. All forms play a role, and in order to utilize that role for matrix health one cannot focus on a singular form of collagen.
· I am only concerned about generating collagen for skin health – the skin matrix like many tissues is a complex array of proteins (and yes collagen is a dominant one), as well as glycoproteins (tenascins for example), and polysaccharides (like hyaluronic acid). They form an intense network of cell decision making and communication and contribute to elasticity, resilience and movement. When one only focuses on collagen one is missing the entire picture of how the matrix works, when and why it is unhealthy and what to focus restorative measures.
These are just a few of the issues and point of confusion that contribute to $8B collagen industry. It has grown rapidly and because of the commercial success there has been little incentive in educating and clarifying the issues. One would expect that eventually consumer dissatisfaction and confusion will mount, haunting this sector unless we bring true value and adequately meet consumer needs.
Microbiome Variants
I have no concerns over the leveraging the advances in microbiome science and formulations. These are exciting times with the potential for significant impact on consumer health and wellbeing. What worries me is the urge to create a never-ending collage of terms to define a product. Consumers understand probiotics, although consumers often understand this as being in reference to “good bacteria”. With some clear exceptions like Gnosis by Le Saffre, we have not spent a lot of educational time and effort explaining that they also include yeasts. Bacteriophages represent another tier of communication that we will need to work at. However all three components, bacteria, fungi and phages form the critical triad of a healthy microbiome.
The term prebiotics, for the fiber-food that nourishes our microbiome is becoming well accepted. However, differentiating prebiotics from ordinary fiber remains a challenge.
Postbiotics refer to the metabolic end products from our microbiome, or even the cellular remnants of probiotics. These elements have a strong place when describing mechanisms of action linked to diet and a healthy microbiome. Consumers will struggle with this, but as formulations use this approach to explain how a microbiome-based product can still work even if the probiotic is dead. This role may engage consumer curiosity. Certainly, there is a need for sustained education.
Greater concerns arise when we create terms for probiotics that have impacts on specific organ targets e.g., brain (psychobiotics) or skin (skinbiotics). Here I think we are moving too fast, and this is creating consumer confusion. Given that the microbiome affects every organ we may end with a flood of nomenclature that may point to the intended target but also create a monster for education as these simple classifications are never that simple. One could ask is it all necessary, or is it just cute marketing for the sake of saying hey, something new here!
When consumers are confused the natural outcome is to hold back from purchasing a product. Hesitancy is not the same as confidence and conviction based on solid knowledge and facts.
The Immune System
The global pandemic rightfully so created a massive discussion and obviously massive consumer demand. Approaches to health that involve the immune system have been historically poorly managed by many. The problem resides that the immune system is not a single system, it is actually multiple systems with numerous checks and balances. Even to the point where different parts may directly oppose other parts. Nevertheless, everyone has been taught we must stimulate your immune system. Actually in many cases we want to do the opposite, we want to calm it down.
In the case of COVID19, while there is a clear pathogen involved and the goal is to remove the pathogen. The problem is that a lot of the tissue damage and mortality results from “friendly fire” damage where a portion of the immune system has gone berserk and attacks oneself in an overly robust manner ( COVID19 and Nitric Oxide). In this case, this disproportionate response needs to be curtailed, with the goal of restoring balance.
Keeping COVID19 as the discussion point, it is this rebalancing act that is behind the benefits of Vitamin D, polyphenols like elderberry, and the vascular actions of Vitamin K2 Vitamins K2 and D3 In managing COVID19. However, for clarity, none are stimulating the immune system, rather they are suppressing the Th1 cellular immune response that is excessive, as is the case in autoimmunity.
Without an intimate knowledge of the immune system, we can create and foster consumer confusion by discussing these situations in the context of “stimulating the immune system” when it is the robust immune response that is driving damage. This is similar to the immune response to the bacteria, Helicobacter pylori, that resides in the mucus layer lining the stomach. The mucosal immune response fails in its attempts to kill the bacteria, given that they lurk out of their reach (protected from stomach acid by enveloping themselves in a cloud of ammonia). The repercussions of this immune response, is that the biochemical weapons used by the immune cells damages the lining of the stomach, creating dysfunction and eventually gastric cancer. We demonstrated that using vitamin C, as a dietary adjunct to limit nitrosative and oxidative stress, can limit this friendly fire and suppression the long term damage to the stomach Vitamin C and gastric cancer .
The DISSERVICE
Melatonin
Unlike many of the botanicals, proteins, fats, polysaccharides, minerals and micronutrients that we consume in our diet and as supplements, melatonin is a hormone. As such, we need to be very cautious about dosing. The pioneering research done by Dr. Wurtman emphasized this, where clinical benefits with melatonin were noted at doses of 0.1 mg/day or 1mg/day tops.
However, as I was once told by a Big Box Store buyer, consumers respond to the perceived value of much higher doses, because “more is better” right. Along the lines of “if 1mg works then 10 mg will be even better”. Product merchants know it was less than ideal, but the goal was to move items off the shelf, so as far as melatonin goes doses of 10mg/ml or more, are what sells.
Here is a classic case of where we really needed to make sure that consumers understood the dynamics and the physiology, and then create products aligned with that knowledge. High dose of any hormone has repercussions, and one of them is to shut down endogenous production. The goal of supplemental melatonin is to support local production in case it is low, thereby improving sleep and managing jet lag. However, doses greater than 1mg/ml is doing a disservice to the consumer.
One could focus consumer education using scenarios that may resonate, noting again, that few appreciate it is a hormone. For example, does one think that a dose of any hormone that is 10-100 times of more of any hormone would be a good idea? One hundred times the dose of testosterone would not have repercussions?
The Natural Products Industry had a chance to offer a solid solution to a significant consumer need, sleep. However, we got trapped in the game of sales and walked back from the goals of improving the health and wellness of consumers. Certainly, there are cases where health care providers do not know the medical literature around melatonin, and this results in poor recommendations. We should be doing better. Those involved in product development who know the literature could play a vital role in establishing a balanced, effective product without complications.
Oral Hyaluronic Acid
One of the alarming features of the Natural Products industry is its pre-occupation with taking pharmaceuticals, for either human or veterinary applications, and repurposing them as dietary supplements. Some products are often touted as the botanical equivalent of a pharmaceutical in order to attract sales. Berberine is a recent example with its comparison to recent weight loss drugs like Ozempic Berberine as a Natural Ozempic
Hyaluronic acid (HA) is a great example of a direct transfer of a drug into a supplement. The original use of HA was as an injection into the knees of horses, as this large polysaccharide acts as a natural lubricant. It is this lubricating function that is utilized by gastropods, enabling their movement. Snails have no feet and so they slide along the ground on a layer of mucus (HA) that reduces friction. The South Korean cosmetic industry has long utilized this functionality in topicals to create a smooth texture on the skin. Works well.
However, the dietary supplement industry has developed versions where HA is ingested and expected to achieve the same lubricating goals as when given topically or parenterally (injection). The problem is that when taken orally HA is digested into thousands of little pieces (sugar molecules) prior to absorption and has no chance of being absorbed intact and execute its desired goals.
Hyaluronic acid is a very large polymer that is massively too large to be absorbed intact. Hence this polysaccharide has zero chance of being effective when take orally. Nevertheless, we do not tell the consumer this. If it sounds good to them, we will sell it. We can do better than that. One way is to develop products that alter the cellular decision making so they create more HA themselves, where and when we need it. That requires a major uptick in consumer education.
Skin and Collagen
I have already discussed the collagen market, under the general banner of “VAGUE” but it could very well be filed here as a disservice. It is not listed here as there are some solid clinical support for select collagen peptides that do have positive benefits, enhancing matrix health and cellular decision making.
For the most part however, we do a terrible job at educating consumers as to the value and importance of matrix health, and how to achieve it. Collagen, collagen peptides, “vegan Collagen” remain ripe for sustained confusion and misinformation.
Pixie Dust & Proprietary Blends
Pixie Dust refers to the habit of using doses of ingredients that are way to low for any viable benefits. Why are they then included? Simple, it is because the name recognition persuades consumers to think that there is true value in the product. They do not know the correct, supported doses so simply on name recognition they believe there is value. In reality, there is nothing there.
Proprietary blends are a coy tool used to try and create some intellectual property over a product that has generic, basic ingredients. Essentially the goal is to block competition from duplicating your product by hiding the precise amounts of individual ingredients behind a wall stating it is proprietary. I appreciate the need to remain competitive.
However, what often happens is that the product is dumb downed behind this wall of obscurity. What some companies do is fill this “proprietary blend” with the cheapest ingredients at the highest amounts and the most expensive at the lowest amounts. This is unrelated to what is needed for efficacy, it is simply an effort to limit costs whilst looking intellectual and special.
Essentially it is active disinformation or at least deliberately hiding the value, or lack thereof, by being vague. Over time these products disappear but they regenerate using the same tricks. If the company will not provide the details of the doses, then take that as a sign that you may not be getting what you want or need.
Poorly Executed Clinical Trials – Incorrect Conclusions
To get a clinical trial published it used to require established criteria of sound execution, design for the purpose, and conclusions that were well supported by the data. With the recent explosion of journals that desperately want papers to publish, the standards have fallen. Often statistical hijinks are used to create a marketing talking point that is in fact, not supported. I see this all too often now, especially with social media being involved.
There is a trend now to smooth over a truly poor clinical study with a catchy, meaningful headline with social media, and hoping that the masses will not read the actual study, evaluate its design, competency, power, and the conclusions that are drawn. This is all too disturbing as here we have the illusion of scientific excellence being used to convince consumers as well as busy healthcare advisors who just follow the headlines. That creates doubt in the value of all science.
I do not see this problem subsiding in the near future. We are left with a challenging environment where we say “follow the science for true guidance”, but in actuality the science may be poor in execution and the conclusions unfounded. Using science to mislead rather than educate and inspire is terribly disturbing.
SUMMARY
This view of the natural products industry certainly has cathartic elements for this Professor and Innovator. I hope that it draws attention to areas that deserve rich accolades, as well as points areas of confusion and why they exist. Finally, it is intended to be frank discussion of misdeeds that are created for the sole purpose of increasing sales and not to improve the health and wellness status of consumers.
This article is meant to invite dialogue and to offer templates, roadmaps for how to create a platform of health. Improving our communication with consumers as to the nature of the problem and how, in specific terms, to implement solutions to address those issues is the key to the ultimate prize – making a powerful difference in health and wellness.