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#04 – Dissenting Opinions on Popular Supplements, Skip the Collagen, Peptides, Metformin, Omega-3 and More with our Industry Insider

How do you know you’re taking the right supplements, or even worse, could your supplements be making you sick? Supplements, otherwise known as nutraceuticals, can have tremendous efficacy for millions of people when taken at the right time at the right dose. However, there are also circumstances where the marketing of supplements far outpaces the science and in many cases, people aren’t getting the quality they are being sold on. In this episode of the podcast, we interview our industry insider who rose to fame in the Most Fish Oil is Garbage post about what to look for in a good supplement and why some of the most popular supplements aren’t always worth your time and money.

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This Episode Covers:

  • FDA regulated supplements manufacturers vs. FDA approved drugs [3:20];
  • Verifying raw material content in supplements and the importance of expiration dates [9:00];
  • Finding a trustworthy supplement brand [15:00];
  • Metformin vs. Berberine and heart health / PCSK9 [23:30];
  • Why more curcumin bioavailability might not be a good thing [29:00];
  • Liposomal supplements and omega 6 / omega 3 ratios [33:00];
  • Peptides and natural repair mechanisms [42:00];
  • Collagen supplements and bone broth – a contrarian view [45:00];
  • Crafting a supplement regimen that works for you using labs [50:00];
  • What are the best omega-3 supplements and are they effective? [53:30]

Show Notes and Discussion:

After the lead off, which mainly focuses on tips and tricks for finding high quality supplements, this episode contains some fairly controversial takes on popular supplements.

Here is my blog on berberine vs. metformin.

Chris was interviewed on the blog on our popular fish oil post as well as a multi-vitamin post. Those blogs layout a lot of his thinking on Omega-3 quality and dose (unless your doctor tells you otherwise, I don’t think most people should mega-dose fish oil, instead my sense is that the dose should be a Barry Sears type protocol that seeks to balance EPA / Arachodonic acid ratio based on lab work).

Here is a great resource for the inflammatory nature of an imbalance between omega-3 to omega-6.

However, we did establish that the dose of omega-6 fats in liposomal supplements is probably relatively small.

One of the “dissenting” takes is on curcumin and techniques supplement brands use to increase bio-availability. To be fair, one curcumin phytosome, Meriva by Thorne, does have some clinical data that is encouraging both for depression and osteoarthritis.

I also wrote a blog post on curcumin bio-availability which can be viewed here. For more on curcumin and turmeric in human studies, this blog post by Aaron is indispensable.

Rat study on piperine black pepper interfering with metabolism of pharmaceuticals.

Human commentary on the ability of piperine to interfere with metabolism of drugs in the liver.

The NEJM study on choline, lecithin and TMAO can be viewed here.

Aaron also wrote a great post on what we know and don’t know about TMAO.

Here is a discussion of the use of peptides for bone and tissue repair.


John: Welcome to the “Gene Food Podcast.” I’m your host, John O’Connor. Today we have a special episode on supplements with a sort of a unique format. This will probably be the first and only time we have an anonymous guest on the podcast, who for the purposes of today’s talk, we’ll call Chris. Chris works at a large supplement brand that works directly with medical practitioners. And he has been featured on the blog in the past on some actually very popular posts on the “Gene Food blog” as our industry insider.

And rather than get his brand involved in sort of the different bureaucratic channels you’d have to go through to do that, we decided to just keep it nice and simple and continue to feature him on the podcast in the same way that he’s featured on the blog which is as the industry insider. So he’s a personal friend. He has great knowledge of the supplement industry. And we get into a number of different topics related to supplements including liposome supplements, curcumin, omega-3s, how to find a good reputable supplement manufacturer, how to avoid certain practices in the supplement industry, FDA involvement in the supplement industry, peptides, collagen. It’s pretty much all things supplements.

There’s some nerdy stuff, and there’s some more zoomed out stuff. So I think there’s a little bit of something there for everybody. Without further ado, here is Chris, our industry insider and I hope you enjoy today’s episode.

So Chris, not your real name, because we have… Chris for the listeners at home is our industry insider who gives us the tips that we use on some of our blogs, like our fish oil blog which is a super popular blog on the Gene Food site, basically giving us how the sausage is made perspective from inside the supplement industry but does not necessarily wanna come out and get the brand involved and get his company involved. Just he and I are good friends from the time I’ve spent in California. Okay, so Chris, so tell us kind of your position and your role in the supplement world if you could?

Chris: As you said, I work with a manufacturer that actually manufactures products specific to or mostly specific to the practitioner channels. So we make products for, we make products alongside, and we sell exclusively to and through healthcare professionals.

John: Right. So it’s basically like medical grade nutraceuticals?

Chris: Correct. Yeah, medical grade, pharmaceutical grade, it’s been called a number of different things.

John: Sure. And so it’s the products that doctors, when they do turn to a supplement, are using for their patients, essentially?

Chris: That is correct.

John: Yeah. And one of the things that we chatted about kind of offline that I think is a good entry point into this whole conversation because we’re gonna get into basically…really a lot of this is gonna center around quality and proof for the supplement industry. Both are kind of big things in the supplement industry. But this role of the FDA in this whole thing and kind of the distinction between a regulated company, FDA regulated company versus or an FDA approved supplement company. How does that play into this whole crazy supplement world?

Chris: So there’s kind of this misconception floating around that we are not an FDA regulated industry, when in fact, we are very much an FDA regulated industry as manufacturers. My plant, in particular, is routinely audited by the FDA. What we’re not required to do is gain FDA approval for our products the way that a drug company would. So we can bring or anybody can bring any product to the market without going through the trials that are required of a particular drug.

John: Okay, so it’s this distinction between your facility versus the claims you can make with the product essentially?

Chris: Right. So it’s more, nomenclature than anything else. But we are very much an FDA regulated industry. But I guess the trouble is there’s a very low barrier to entry in our industry, right. So I mean anybody can open up shop in their garage and start encapsulating raw materials and throwing them in a bottle and selling them. The FDA they’ve been very clear in stating this is that they don’t necessarily have the manpower to police this industry the way that they would like to. So they’re generally not getting involved until a consumer gets hurt or a consumer has some sort of adverse reaction to a supplement.

John: Okay. And with the FDA regulated facility, is that something where a company like yours invites in the FDA? Or does the FDA choose a select number of facilities that they then choose to go inspect? Or how does that work? What is the concert between your team and the FDA work in these cases?

Chris: Correct, yes. It’s essentially an audit, we’re audited by the FDA. They announce they’re coming, they show up a period of time later and tour the facility essentially. And they work off of a very specific checklist.

John: Okay, right. And so pharmaceuticals, FDA approved based on rigorous or depending on what your sort of opinion is of the pharmaceutical industry. Of course, there’s a huge role for pharmaceuticals in medicine, but that’s something where a specific pharmaceutical drug will get approved. But in the supplement world, one of the ways it sounds like to identify a quality provider is to try to find out which supplement manufacturers have had their facility audited by the FDA. Is that something that…? How do you find that out?

Chris: You would have to reach out to the manufacturer directly which in many cases can be very difficult to do in this industry. Because a large, large majority of products that you’re gonna find on retail shelves are simply repackaged products, or they’re working through contract manufacturers. So if you can identify companies or products that actually manufacture their own products, it’s much easier to kind of work upstream from there and get a little bit of transparency, a little bit of insight into the way that their manufacturing facility works and you know, what the FDA’s role is there.

John: Okay, so speak to that, for the people that don’t know. I mean, this is an interesting thing about the whole supplement world. When I think of the supplement world, I think of a bunch of brands that I consider to be very high end and sometimes that varies by product. I also think of the whole affiliate world where you have companies that create products that have maybe 2%, or 3%, of an ingredient that has shown efficacy and the rest is filler. So, therefore, they have a huge margin. And then they can pay a massive rip to armies of affiliate marketers to then push that product on Facebook with different internet marketing schemes. What about those players and also the contract manufacturers? Just tell our listeners what they need to know about the hierarchy in this case.

Chris: Yeah, you can create a company, create a brand, you can reach out to a number of different… and they’re very… there’s plenty of them out there. Contract manufacturers that will put together products what you’re hoping to be very specific to formulate the formula that you have kind of in mind, or that you have put together. And then from there, there are ways to….so this kind of comes back to… There’s a lot of self-policing in this industry, right.

And you’re relying kind of a lot on the morals of these individual companies to put together products the way that they should be put together. And so when you talk about kind of Pixie dusting or sprinkling in marginal amounts of specific raw materials, there are still way that, you know, though, for instance, stability testing, to verify the actual content of active raw materials in these formulas. And these are documents that should be available through the manufacturer.

So if you’re a concerned consumer, you should actually be able to reach out and request certificates of analysis, requests, some of the stability data. Things that are going to verify the actual raw material content. And then furthermore, verify that these products if they do come with an expiration date, which is entire nother conversation on its own, but they should be. And if they are coming with an expiration date on the bottle, that that label is meeting the dosages that it’s claiming through that date of expiration. Verifying that you’re getting what you should be getting at the doses that you think you’re getting.

John: Okay, so those are some good points. So there’s a little bit to unpack there. So one of which is, you know, the best brands… And we see this as we do analysis of for example, like fish oil. In the fish oil post that you helped us with, in the interview we did with you. One of the products that we came to like is Nordic Naturals because they do publish certificates of analysis for each batch of fish oil. And there’s major…which we’ll get to omega-3 in a minute. There’s major problems with some impurities in omega-3 products.

Another one that’s come on our radar is Rosita I believe I’m pronouncing it correctly, which is a Norwegian brand of cod liver oil, which seems to me to have very stringent testing. But you’re saying certificate of analysis, and then also… And you and I have chatted about this so I know where you’re headed with this. What I hear you saying is the dose of let’s say, vitamin C, in a supplement is not gonna stay the same as the supplement sits on the shelf. Can you tell listeners sort of how that works?

Chris: Right. So all raw materials degrade over time, right, and some are gonna degrade faster than others. What a manufacturer should be doing on their end is understanding these rates of degradation and appropriately manufacturing with dosages that are going to account for this rate of degradation through the shelf life of the product. And then having the data to back this claim up.

So kind of even taking a couple of steps back from that the FDA absolutely requires drug companies to do stability testing and label products with an expiration date. Doctors need to know that when they are prescribing you know, just call 10 milligrams of ingredient x that the patient is getting, at minimum 10 milligrams of ingredient x. The doctor needs to ensure this to get consistent clinical outcomes or predictable outcomes with this patient.

The FDA doesn’t require supplement companies to do this. We have two options, we can kind of follow suit with the pharmaceutical companies and do stability testing, and label products with an expiration date. And we can verify those expiration dates through stability testing. Or we can label products with a manufacture date. So you’ll see things like you know, you’ll see manufacture date, manufactured on or on date.

What that is implying is the supplement company is essentially no longer liable for that label past the date of manufacture. So you can go back to your vitamin C example, let’s just say 100 milligrams. We know that vitamin C or ascorbic acid degrades at a rate of 14% year over year over year. If we were to create a supplement that we were gonna put a manufacture date on, we could manufacture that product and put exactly 100 milligrams of vitamin C in that product, verify that, put that date on the bottle and send it out to our…wherever it’s going for retailers.

So two months, three months, four months from that date, there’s no longer 100 milligrams of vitamin C in that formula. And you really don’t know what is in that formula. Generally, the faster that raw materials degrade, the more often you’ll see manufacture date. So the probiotic industry is notorious for manufacture dates on their labels because they tend to degrade very, very quickly.

As toward going back to vitamin C example, if we’re putting an expiration date on that bottle, we need to make sure that through that date, we are meeting label claims. So there’s a minimum of 100 milligrams of vitamin C at that day of expiration. So we actually need to manufacturer with an intentional overage, right? So we’re putting additional raw material in there to account for these rates of degradation to make sure that we’re meeting label claim.

John: Interesting. So at the end of the day, when you see a mega dose in certain supplements from a quality manufacturer, it’s partly there because of the recognition that that supplement ingredient is going to really degrade over time. And when I think of the probiotics, I think, okay, well, that could be part of the reason why in so many studies, when people look at probiotics, they show that there’s no real traction on the part of the strains in the microbiome. Because who knows at what stage they’re getting the probiotic supplement, right? Or somebody who’s even home testing, like with biome or something like that.

So that’s a very good actionable point looking for the expiration date as opposed to the manufacturer on date. What about like good manufacturing practices or anything else listeners can look for in trying to find supplements that are gonna be trustworthy?

Chris: So if you are an FDA regulated manufacturer, you are adhering or you’re required to adhere to Good Manufacturing Practices drawn out by the FDA. So it’s not necessarily something a stamp that’s required to be seen on the bottle. In large part, I think if you’re working with reputable manufacturers, good manufacturing practices are in play. There’s a number of other third-party… I’m blanking right now. But you see things like…

John: IFOS and stuff like that.

Chris: IFOS, non-GMO so different third-party certifiers that’s the word I was looking for…who essentially have kind of their own set of standards. And then a manufacturer will pay them to then come in and essentially audit their facility to allow them to put that stamp on the bottle. So I think those are valuable especially in the retail industry. I just don’t know that I would necessarily weigh my decisions on finding these specific third-party certifiers.

John: It sounds like the Good Manufacturing Practices piece is one way of kind of like meshing with and flushing out whether they’re also FDA audited.

Chris: Right, exactly. If you’re FDA audited, you are adhering to Good Manufacturing Practices.

John: Also based on conversations we’ve had, and we did some stuff with the blog on multivitamins and things like that. I know one of the things that you’re big on too is, you know, even aside from just looking for the way things are manufactured, like certificates of analysis, you’re big on even just like what kind of mineral blends do they use. If you look at a brand and they’re using certain types of minerals that signals quality as opposed to other types of minerals, which might signal something cheaper. So can you talk about what are kind of these like caviar of minerals that you can find in some of these supplement blends that would make you trust more than some others?

Chris: So in my opinion, if a company is doing their due diligence and sourcing quality, raw materials, in all likelihood, they’re doing everything right behind the scenes. So minerals are a great place to initially look to kind of flesh out the potential quality of the particular product. One thing that I always wanna see with my multivitamin, for instance, are chelated minerals. So if you look at some of you’re cheaper multivitamin options, you’re gonna see things like calcium carbonate, magnesium citrate. These heavy mineral salts essentially are very, very cheaply sourced.

And in turn, they generally have very poor bioavailability and can be associated with some of the GI side effects, the unwanted side effects associated with taking a multivitamin. However, if you see things like magnesium glycinate, or calcium glycinate, these true chelated minerals. Or even go a step further and potentially look for products that are specifically sourcing their minerals from a company called Albion. That is I think a great indicator and kind of a great starting point when looking at your products in identifying what’s gonna be a quality product, essentially.

John: I think that’s a great point. And then another thing that I’ve been looking forward to since we started chatting and just learning from you and kind of the conversations we have is… And the other thing that’s crazy is I look for this and I almost never find it, which is a little discouraging. But speak to USP grade, because like I would love to see every single supplement manufacturer…you know, vitamin C is included in a ton of supplements.

But it’s so rare that you’ll find a supplement manufacturer that uses USP grade vitamin C. How important is USP grade in your analysis of these different supplement brands and their products and their quality?

Chris: I think it’s definitely important. So USP or United States Pharmacopeia, they’re kind of a third party watchdog, if you will, they kind of set the standards for purity, potency, quality of these individual raw materials. However, there is a caveat, right. So going back to vitamin C, you can find vitamin C, as a manufacturer, extremely cheap. You know, we’re talking, you know, 15, 20, 25 cents per kilo. You can find USP grade vitamin C, for you know, maybe, double that. And then you can go upwards of $1 plus, per kilo.

What’s important… and again, this comes back to the responsibility of the manufacturer. USP continually updates their monograph. So they’re constantly evolving and changing what they’re looking for with these specific raw materials. So you can have a USP grade raw material that is adhering to a monograph, you know, that is 10 years old. Or you can have a USP grade raw material that is adhering to the most consistent updated monograph. And it’s also important too if a company is going to label a raw material USP grade, a) they’d have to buy a USP grade raw material. But then, b) in their own lab, they have to verify that that’s actually a USP grade raw material. So there are some additional steps involved.

John: So there’s a layer of bureaucracy there that maybe makes that a little bit less important. I would assume, just from a business case standpoint, a lot of manufacturers are not gonna wanna go through that. That sounds to me pretty onerous.

Chris: Right.

John: And especially for these companies that are, you know, just kind of doing this in a much more informal way in small batches, as well, like kind of the white labelers and stuff like that. So I’m somebody who definitely takes supplements, and I believe in supplements. I take supplements, situationally, I take certain supplements for travel. But I also take time off from supplements. It’s not like I’m… I don’t take like huge amounts of supplements, and I tend to cycle them.

And I feel like there’s people out there that are just…. Look, everybody’s trying to feel good. Everybody’s looking for an advantage. The whole bio hack community has become a big thing and that’s cool and great. But my sense of things is that there’s probably a component of people out there that are taking so many supplements that they don’t really have any idea of what’s like efficacious for them.

And so what I wanna do is kind of get into some of this stuff we’ve chatted about in terms of some of the top headline supplements, what your take is on how well they work, efficacy, what you’re seeing with your company and the people that are consuming your products. And kind of just get a little bit in the weeds on some of these more popular ones. And the first thing that I wanna jump into was Berberine and Metformin and all this blood sugar stuff.

And you know, I know a guy here in the city who takes Metformin prophylactically. And for the listeners who don’t know Metformin is this really cheap pharmaceutical drug that basically helps regulate and control blood sugar and some people take it as like an anti-aging and it’s sort of an anti-cancer product. But it’s my understanding, Chris, is that Berberine a nutraceutical works just as well as Metformin. What’s your take on this topic?

Chris: So if you go back and actually look at that, there was a comparative trial done, essentially, a gram of Berberine against a gram of Metformin, and they were very consistent drops or very comparative drops in both blood sugar and hemoglobin A1C. So from a metabolic standpoint or a bio….looking at these different biomarkers, you can potentially… and I will say not everybody responds to it as well as, you know, another person and there’s potential reasons for that.

But you know, Berberine is potentially one of those direct comparisons against a very popular pharmaceutical. The challenge that I face in talking with doctors, is that you’re right, Metformin is…they’re cheap. And there is kind of this growing longevity crowd out there that is micro-dosing Metformin essentially kind of viewing it as a multivitamin so taking it prophylactically. And that’s more for… I don’t know, if it’s so much for its ability to suppress blood sugar or keeping A1C down as it is through the way that it’s working through some of the different pathways, biochemical pathways, specifically, AMPK which is kind of one of those…along with your sirtuins, one of these longevity pathways that is being looked at in that role.

But yeah, Berberine is a very, very popular in even the practitioner channel. More and more people grow very wary of the drugs that they’re taking they wanna move away from the pharmaceutical approach and sometimes try these more natural approaches first. Berberine is definitely atop that list.

John: Yeah, and the thing that’s interesting about Berberine and too to piggyback on that is you have the blood sugar stuff is probably maybe what it’s potentially best known for. But there’s all that liquid stuff out there on Berberine too. I mean, are you seeing any…in your little corner of the world, is Berberine use motivated by blood sugar? Or is it motivated by lipids? Or is it motivated by both?

Chris: You’re right, you’re seeing more and more of this lipid application of Berberine where historically it… Well, it first kind of came out in the scene as an antimicrobial and then it shifted more towards blood sugar. But I think with the attention that some of these new pharmaceuticals or these PCSK9 inhibitors are getting in their ability to dramatically lower LDL. They’re finding that Berberine working through that same mechanism, so your PCSK9 inhibitors are essentially blocking this enzyme responsible for breaking down LDL receptor sites. So you kind of keep the liver open longer if you will open for business able to bind and clear more LDL particles out of the blood. So yeah, people are seeing very nice drops in LDL when supplementing with Berberine.

John: Yeah, that’s really cool man. We got big into PCSK9, I don’t know if you…this is maybe a little too obscure. But there’s this some… I’ll text it to you if you haven’t seen it. But there’s a study called the Retterstal study, which was done in Oslo, which basically took like 39 healthy people and did a controlled trial put them on a ketogenic diet. And one of the genes that they looked at, there was an incredible variability in their response to a high-fat diet. Like people’s LDL cholesterol went up between 5% and 107%. And PCSK9 was right at the top of that list.

So that’s super interesting that that’s on your radar too because…You know, the thing that’s funny is, it’s very rare that somebody has a favorable PCSK9 variant or family of variants. And I’d have to get Aaron on who’s our geneticist to speak to the exact statistics. But I think it’s something only like 10% of people naturally carry variants of PCSK9 that would in a natural state give them that increased LDL receptor activity that you’re talking about. And I had forgotten that Berberine was impacted on PCSK9 so that’s super interesting.

Chris: Right.

John: And so just to tie up the bow on Berberine, it’s not made from a standard plant, is it? Isn’t it like a plant cocktail?

Chris: Yeah, you’re correct in that. It’s really derived from rhizomes of several different plans.

John: Okay. And it’s like, what Goldenseal or something or isn’t it like China origin species of plants? Where are these plants growing?

Chris: So depending on what plant is being sourced, they are gonna be indigenous to a specific region. And actually, that’s an important component in sourcing some of these botanicals or phytonutrients is the regions that they are sourced in. Because different climates different times of year are going to yield plants with different medicinal activity or medicinal properties.

John: Okay. When you said phytonutrients, it made me think back to… God, it would have been like a year and a half ago now or something a conversation you and I were having. You’re the guy that turned me on to this, I had no idea. You know, you go on like… and look, it’s all good. Like, again, people are just out there just to be healthier, and I think that’s amazing. But you’ll see you know, different nutritional blogs and stuff where they’ll add like a little bit of turmeric to a smoothie and then they’ll crack some pepper in and stuff. And it’s like, well, yeah, there’s these studies on black pepper increasing the bioavailability of curcumin in turmeric. But tell the audience your take there because it’s pretty unique.

Chris: So turmeric is one of these phytonutrients that… The conversation has completely shifted away from efficacy or clinical results and it has completely gone towards more this form of conversation of increasing absorption or increasing bioavailability, right. And that’s the way that companies are now marketing these new products, enhanced turmeric or enhanced curcumin. Even going back to the ’70s and ’80s when they really started looking at turmeric, curcumin was one of these first compounds that we could isolate. So it just kind of became the compound of interest.

And in doing so, I think what we’re starting to see is maybe we might have really missed the boat on some of these other compounds within turmeric that clinically could have a lot of benefits as we become hyper-focused on curcumin. And now we’ve become hyper-focused… because it’s well known that this it’s very quickly metabolized. 95 plus percent of all curcumin that we ingest is immediately detoxified from the body regardless of how well we can get it across the gut lumen.

And so this hyper-focus that’s been put on increasing absorption of curcumin, may be negating some of the benefits. And some of the different ways that you know, we’re doing it, whether it’s through liposomal deliveries, or it’s through pairing it alongside something like black pepper extract or piperine, which as you alluded to, there are some potential concerns there in that essentially the way that piperine works to enhance absorption or enhance the bioavailability of curcumin is it slows down detoxification.

So I believe specifically, it’s the…and I may be wrong here. But 2a4 enzyme that’s kind of really responsible for beginning the process of detoxifying curcumin from your body. The challenge with slowing that down is that it’s also responsible for detoxifying a number of different compounds from the body. So while yeah, you might increase levels of available free curcumin in the serum, but at the same time, you may be inadvertently increasing levels of other things that we don’t necessarily want to slow down detoxification of.

John: Yeah, and you said… and correct me if I’m wrong. But I thought it was that in certain circumstances, especially for people that are taking a certain pharmaceutical drug, that taking higher doses of piperine, black pepper alongside those could actually slow the metabolism of those drugs.

Chris: Correct. It’s quite an extensive list and even a very common thing that we’re taking over the counter like ibuprofen, that it’s slowing the metabolism of so you’re kind of potentially inadvertently increasing levels of these compounds that we have circulating in the body that are meant to be metabolized.

John: Yeah. So when you get into the whole world of curcumin too another thing that I think is interesting… And look, I wanna preface this by saying that, at the end of the day, I’m not sure that in many people or maybe even in most people, this is gonna be some huge thing. However, I think it’s something that certain people might wanna be aware of which is the fact that a lot of these, take black pepper and put that to the side, a lot of these curcumin formulas are being paired with phospholipids, and specifically, they’re being paired with like Lecithins and like Phosphatidylcholine, and they’re these omega-6 fats.

So you’re taking these liposomal formulas of curcumin, and maybe then alongside you’re taking liposomal glutathione and those Lecithins have been shown to be converted in the gut to TMAO and other compounds that in certain individuals if those compounds became elevated could be atherogenic meaning they could be bad for heart health. And not only that, but you know, one of the things that I’m super interested in right now is the fact that the conversion of these omega-6 fats downstream to things like arachidonic acid and other inflammatory pathways that can be turned on by having a balance of omega-6 that’s higher than your omega-3 intake.

Now, as a practical matter, is taking some liposomal curcumin going to like throw off that balance in some crazy way? No, but most people aren’t aware of it and some people are taking super high doses over long periods of time. So what do you think about liposomal delivery in general?

Chris: Well, I think you make a good point there. I think going back to whether…you know, like using curcumin as an example or any phytonutrient, resveratrol, coresatin, even Berberine, we’re starting to see these products come to market that are trying to utilize liposomal technology or deliveries to enhance absorption of these compounds that have fairly poor bioavailability.

And the trouble with that is and what we’re starting to see is that it’s not so much these active compounds, once they hit the serum that have the potential therapeutic benefit. But it’s the interaction with your gut bacteria, and the literally dozens, and dozens, and dozens of metabolites that are generated by this interaction when they come in contact with something like turmeric that have very promising therapeutic potential. Whether it’s ferulic acid, or it’s aromatic turmerone in the case of turmeric, like I kind of alluded to earlier kind of this hyper-focus on curcumin, and pushing as much curcumin as we can into the serum, we might start seeing this kind of step back.

Actually, we’re already seeing it with turmeric specifically is companies actually releasing curcumin free turmeric products. And kind of letting the body interact with these things the way that they were intended to and reaping the potential benefits or the noted benefits, I should say, of some of these other metabolites they generate. So basically, when you try to force something or change the way that these compounds are interacting with gut bacteria, like pairing it alongside a phospholipid, it does potentially change some of the therapeutic benefits that you could receive from these compounds.

John: That is…

Chris: And one thing that’s interesting to note…

John: Go ahead.

Chris: I was gonna speak to the actual the relevancy or the efficacy of these products. One thing that has been very interesting and we’ve been asking this question a lot of companies that have come up…and I keep kind of going back to curcumin because it’s become such almost polarizing topic in this industry. Going to these companies and asking them for actually efficacy data.

They have you know, data, after data, after dataset showing enhanced absorption or bioavailability, and a lot of that can even be very misleading. But we still have yet to see any head to head trials putting an enhanced curcumin up against, you know, what’s long been considered the gold standard, you’re 95% standardization or even a straight turmeric. And getting some sort of demonstrable increase in efficacy. Like these studies don’t exist. And if they do exist, we’re not being shown the data because it’s potentially not beneficial to some of these companies.

John: That is an amazing point. So what I hear you saying is essentially that a small amount of turmeric mixed into food or whatever the case as it would have been used for years and years and years, can set off a metabolic cascade just based on small little touches of it, that sets off downstream processes that may be at the root of the benefits of some of these products. And mega dosing it and having these huge amounts as we’re prone to do in the Western world, you know, supersizing it as it would be, you know, kind of the fast food attitude towards supplements is actually becoming demonstrably ineffective or at best it’s ambiguous.

Chris: Right, at this point, it’s made for nothing more than really a cool marketing piece.

John: Yeah, as you would say, like the marketing kind of outpacing the science. I don’t know, man. If I just had to identify the biggest issue in nutrition and supplements just in my bias… and of course, there’s a lot of them but I’m just gonna throw it out there. Somebody told me, I had to name one thing, I would say that it is basically lecithins, vegetable oils, you know, processed omega-6 fats, highly delicate, damaging omega-6 fats that is basically at the root of a lot of disease. And there’s no reason why that… And here’s an interesting question for you just to wrap up this curcumin discussion, this liposomal discussion. Do you have any idea of the amount of, for example, lecithin or these fats like in terms of like the dose that you’re getting if you’re taking a lot of liposomal supplements?

Chris: You know, I don’t, I would… you know, it probably comes down to single-digit milligrams. But I don’t know the exact.

John: Might not be playing that big of a role in and of itself. But I think it is important for people to be aware. And probably more so for them to be aware of the processes you’re talking about, which is a little can go a long way. The megadose is not always the best dose. One other thing we wanted to get into and talk about because it’s super popular right now in anti-aging circles, a lot of people are talking about it, are peptides. So what are peptides? What peptides are you looking at and seeing on the rise? And in what circumstances are they being used?

Chris: Well, in a lot of instances, peptides are essentially hormone precursors, so kind of going a step back. And a lot of times, these aren’t supplements, these are injectable, administered by healthcare professionals. We might be able to influence, you know, for instance, growth hormone production by supplying the peptides responsible for construction of these hormones. One peptide that I’ve become particularly interested in is collagen peptides.

And then even kinda like to take it a step further, there’s you know, a German laboratory called Gelita that’s developed a very specific set of peptides derived from a gelatin hydrolysate that has shown some very promising results in the world of both soft tissue support so joints, tendons, ligaments, skin. And then also kind of [inaudible 00:41:26] in the cosmetic industry. Do you want me to kind of dive into the mechanism of how these things are working? Or do we have time for that?

John: No, we’ve got time, we’ve got some time to get into the whole peptide thing. Yeah, I mean, so what are the…let’s say person x comes in and is gonna be administered one of these products. Who’s administering them first of all? Is this like MDs, like physicians that are administering this to patients? Who’s administering collagen peptides and why?

Chris: Generally yes, I mean, there are retail products available out there and there are specific things that you can look for when identifying these peptides. But in many cases, where some of these raw materials just because of the absolute need, especially with today’s landscape is in the world of pain management, and joint care, and addressing various tendinopathies and tendinitis. And trying to get people away from the standard of care when it comes to pain management, your opioids, and your [inaudible 00:42:31] and your over the counter type II inhibitors.

What’s really cool about some of these studies is they’ve actually shown the potential to begin rebuilding some of these tissues in patients with pretty significant degenerative processes in place. To take, you know, osteoarthritis, which is essentially a degeneration of cartilage tissue. By ingesting these specific peptides, you’re essentially looping into the body’s natural repair mechanisms. And by presenting these are what are essentially pre-digested proteins that are able to get through the gut lumen intact and have a very high affinity for these different connective tissues.

So they’re settling in joints and they’re presenting to chondrocyte as degraded tissue. And kind of eliciting this response, the same response that they would if these chondrocytes were naturally coming into some broken down tissue or degraded tissue. So they’re actually stimulating endogenous production of collagen, and aggrecan, proteoglycan, these proteins that are critical components of the structure of these tissues. And you see the same thing in the skin with fibroblast and then the tendons with tendonitis. So it’s some pretty cool stuff with these peptides, and I think you’ll start hearing about it more and more, as both doctors and patients and consumers look for alternatives to what’s long been considered standard of care within the pain model.

John: Interesting. And do you know the amino acid breakdown of some of these collagen peptides?

Chris: I don’t know the specific amino acid breakdown, I might be able to get that to you. I would say in general…you know, collagen is good in moderation. With these specific peptides, you’re able to get a lot of efficacy out of smaller doses. We kind of go back to this Western approach of more is better of everything. That’s not necessarily I feel to be the case with collagen. And viewing collagen as a primary protein source, which, you know, some people do nowadays, because of the marketing that’s driven in this industry.

John: It’s everywhere man, collagen, collagen, collagen, collagen protein bars, eat your collagen, drink your collagen it’s crazy. Bone broth, gotta have the bone broth, collagen, collagen. Yeah, it’s just a…

Chris: Right, people are consuming 50, 60, 70 grams a day from the perspective of looking at it amino acid complex it’s not…there are proteins out there that are much, much better. But from the clinical application of this product, more specifically, you know, you can look for a raw material that I’m really, really impressed with is branded Forte Gel. And again, this is a raw material out of this German laboratory with a lot of really, really good human clinical data, demonstrating efficacy at low doses.

So we’re talking five to 10 gram daily, versus, you know, what your single scoop of store-bought collagen is gonna provide which is 20 grams, 30. You know, people are ingesting crazy amounts of collagen which isn’t necessarily better. It’s not necessarily safe long term because of that amino acid structure.

John: And that’s why I was trying to remember what the amino acid structure is of the collagen because you know, it comes up in every single…it comes up all the time now in these conversations is the Volta Longo Research about you know, the inflammatory nature. Just constantly in my mind thinking about these nutrition conversations, the inflammatory nature of certain amino acids in particular, and how they can contribute to you know, the increasing growth factor. And then that increases these different bad growth pathways in the body. Is that the reason why you have concern about the excessive increase of collagen? Or is it something in addition to that?

Chris: Two specific amino acids that I look at when I have concerned with collagen, it’s very high in proline. Proline downstream has the potential to increase oxalate kidney stone production. Secondly, is Histidine. As patient’s histamine loads and their potential for food allergies increases with that Histidine can be directly converted into histamine. So patients who have multiple food sensitivities or they’ve been tested and have shown to have elevated levels of histamine in their gut, they’re gonna want to limit collagen intake.

John: Yeah, even if they have allergy or one of the things that we see. You know, early on, I think Aaron has given a science score that’s somewhere in the middle. We’re not here to say that this is established science yet you know, there’s more than needs to be done to do the research here. But to piggyback on that, you know, if you’re somebody who has a lower ability to clear histamine because you have lower levels of Diamine oxidase or you said, you know, ibuprofen. You’ve done things that impair your body’s ability to clear histamine. Maybe you have allergy, maybe you’ve had a course of antibiotics that you’ve taken.

And then you listen to a blog or a podcast and they just say with no caveats. “Go take collagen, it’s amazing for you just eat it, eat it, eat it, it’s amazing. It heals your gut, it heals your gut.” And you feel like shit after you took collagen, well, there’s your reason why. So, I mean I think at the end of the day… I hear about this stuff, like Forte Gel, it sounds amazing, it sounds exciting, low dose. And I also am thankful that it also sounds like in this case, there is a gatekeeper to taking these products, which is the physician correct?

Chris: You know, you may be able to dig around and find it in retail as well. But yeah, a large majority of collagen products with very specific application, in the practitioner channel, you’re going to find Forte Gel.

John: Okay, interesting. Yeah, I like… you know, for what it’s worth, it might not be worth a ton. I mean, different people have different perspectives on this I appreciate that. My sense of things is that I think that the lab information needs to really be democratized. And people need to have a lot more access to their labs because of the fact that you know, for something like an omega-3 supplement, it’s like, why are you taking an omega-3 supplement? Are you deficient in EPA and DHA? Do you wanna bump up your EPA and DHA levels or are they adequate?

And you know, in most cases, people are supplementing without the benefit of the bloodwork. Are you taking a methylated B vitamin because you wanna bring down homocysteine? And it would be great if we could have the democratization of the lab data. But I think a little more in the way of prudence and a little more of a conservative approach when it comes to some of these supplements because these are powerful things.

I mean, as a take-home message for people, I mean, what’s your sense of self-experimentation? And what’s your message to people at home that are in the experimental mindset, and how best to craft a supplement regimen that’s gonna work for them as opposed to against them?

Chris: Right, I think as you alluded to, like if you can directly correlate what you’re taking with you know, labs, labs are ideal, actual markers. In some cases, symptomatology is enough to go off of. I think if somebody takes something and they feel a difference and they feel better from it, hey, I’m all for it. I think your absolute best bet is to seek out a practitioner who specializes in the application of supplements and kind of work with them…

John: To dial it in.

Chris: …to put together a regimen that’s going to be very specific to your needs. Because you’re right with Dr. Google out there, there’s this plethora of information available, and I fall victim to it too. I’m sure you do. The more you…

John: I do too 100%.

Chris: …the more you read, the more you know, the more you wanna take and before you know it you’re taking 20, 25 different supplements every single day

John: 100%. And that’s a great point. And that’s a point to emphasize. I’m saying this as somebody who has done this. I have taken a ton of different supplements and it’s because I’m reading study A, B, or C and I’ve done that for a number of years. And I’ve taken a bunch of stuff, and I found some of it to be very effective, and I’ve found others to be not as effective. And the conclusion that I’ve come to is that yeah, I take supplements, a lot of the times I’ll take a half dose. I think the dosing is very arbitrary in terms of they’re putting 100 milligrams of L-theanine into a capsule when the studies on theanine show that they get the increase in alpha brainwaves at 50 milligrams. But it goes back to your point about more is always better.

So I’ve just found through a lot of trial and error and doing a lot of dumb stuff with supplements myself a lot of dumb stuff, that I just do better when I take fewer supplements at conservative doses for very specific reasons. So yeah, 100%. I’m right there with you. Is there any…

Chris: I do feel like.. sorry.

John: Go ahead.

Chris: I think foundationally, there are things that we can take. I’m an advocate of taking a multivitamin. I’m an advocate of taking some sort of daily omega-3, I’m an advocate of vitamin K2 as well, as a probiotic. I think these are things that…you know, in speaking to a multivitamin, there are… you know, regardless of how meticulous you are with your diet, there are inevitably deficiencies that are going to take place. Because of the way food is grown in this world or in this country, the way that food is prepared. And I don’t take a multivitamin to you know, think that it’s going to extend my chances of surviving the next five years the way that these things are often studied. I take it just optimize things, right, just to make sure that my nutrient levels are optimal.

John: The omega-3 one is an interesting one because I have been taking an omega-3 supplement, but I’ve been doing it because I actively am trying to balance my EPA to arachidonic acid levels. Because I think that that from what I’ve read is an important marker of inflammation. And we’re just getting so much omega-6. I know I have a genetic polymorphous that basically hyper converts linoleic acid into arachidonic acid. So, you know, drinking some of our own Kool-Aid at Gene food. So I’m doing it based on my lab.

We’ll touch on this real quick here to close out the conversation because there’s a lot of people interested in the omega-3 stuff and that’s how you kind of rose to fame on the blog anyway. Long term data on that seems like really not conclusive. What’s the case for the omega-3 and in what form? Are you taking krill oil? Are you taking algae oil? Are you taking cod liver oil? Like what’s your omega-3 position in terms of supplementation?

Chris: So I’m taking a…derived from small fatty fishes, so sardines, anchovies, mackerel. And I just wanna make sure…one take-home point, make sure that you’re getting your fish oil in the triglyceride or the re-esterified triglyceride in this case. There’s a lot of different forms available on the market, a lot of different oils, a lot of different gel caps. The most important thing I think we can take away from data is that the re-esterified triglyceride is this superior to all other forms, the ethyl esters, phospholipid or what you’re getting with your Krill Oil.

Which is actually…it’s not that I don’t dislike the phospholipid or the krill oil, it’s just the amount that you need to take in order to achieve any type of therapeutic dosing. The amount of actual physical soft gels that you would need to take. And I guess it’s kind of…to circle this back to what you mentioned about some of the inconclusive data. I think you have to look at a number of different factors in this study. A, duration. They’re oftentimes studied in a drug model where you take a population or you take a cohort of patients, you take a very specific timeframe, it might be two years, it might be five years. You administer a dose and you look for some sort of hard outcome. So, for instance, increasing survivability over a five year period.

You know, that’s not the reason that I supplement. That’s not the way that a lot of these natural ingredients are working. And so they can’t be studied like that and you can’t assume that they’re gonna provide a drug-like outcome in a lot of these instances. And in most cases, we’re not specifying form. So omega-3s, are we looking at ethyl esters, are we looking at re-esterified triglycerides?

Dosing is generally…if it’s even mentioned, it’s very, very low in the studies, it might be 250, it might be 500 milligrams. Where we’ve actually seen some really good data as far as you know, reduction of triglycerides or improving mortality at much higher doses. So it’s just a matter of being able to efficiently achieve doses in grams rather than milligrams, which are oftentimes what are studied. And really doesn’t have any effect on a diseased patient population. So if you take 500 diabetics, and you give them 200 milligrams of EPA and DHA, it’s probably not gonna do much for them. But you can create a very kind of negative headline based on that trial.

John: I hear that. I think also part of it has to do with this whole issue of like niacin and heart health. Now, I know that niacin has recently fallen out of favor for Lp(a) with some of the really smart lipidologists. But when you look at the two contrasting niacin studies that were done in the “New England Journal of Medicine,” one of them looks at people that have elevated lipids like hyperlipidemia, they have elevated LDL cholesterol, they have low HDL cholesterol. They take niacin. Their LDL cholesterol comes down from a point of elevation and their HDL goes up from a point of, you know, being in the basement.

But then they take people who are already on a statin who have super low levels of you know, LDL cholesterol based on being a statin, then they give them niacin. They’re like “Oh, niacin didn’t lower their LDL cholesterol.” The reason it didn’t lower their LDL cholesterol is because they’re on a statin already. And so it’s like maybe the case here is with the fish oil stuff to your point, maybe you need to dose it appropriately, and dose it appropriately based on what your labs tell you.

I think maybe there is a case for mega dosing for certain people who have brain injury or depression or whatever. But it’s like I think you definitely wanna do that alongside your doctor. And talk to your doctor first before you go start taking huge high doses of fish oil. Why don’t you take cod liver oil if…because cod liver oil, in my understanding, has the vitamin K kind of like naturally occurring? What’s your take on cod liver oil?

Chris: The challenge with a lot of these oils is being able to achieve [inaudible 00:58:51] taste, but also being able to achieve what I feel is like a therapeutic range and the amount that you actually need to take. It’s pretty significant. I haven’t looked at the exact EPA, DHA content of some of these different cod liver oils, but it’s generally pretty low milligram to milligram. For instance, when you take a highly concentrated re-esterified triglyceride, where you might be able to pack 900, 1,000 milligrams of EPA DHA into a single gel cap.

John: Okay, so you’re just gonna get a better…it’s just better dosing?

Chris: [Crosstalk 00:59:25].

John: Yeah, better dosing. Okay, cool.

Chris: Yeah. For me, it’s a compliance issue.

John: Sure. Well, hey, this has been an awesome conversation, man, I really appreciate you coming on the podcast and giving me the opportunity to pick your brain. Tons of really good information about supplements. Maybe what we’ll try to do is kind of do one of those like…remember back in the day on expose from the cartel. We’ll try to granulate your voice so that nobody can tell who you are so you remain the industry insider on the Gene Food blog. But all kidding aside, thanks a lot, man. Really, really good stuff.

Chris: Thank you, John. I appreciate it. Thanks for having me on.

John: Yep, have a great week. We’ll talk soon. Bye, Bye.

Chris: Bye.

John: The “Gene Food Podcast” is our attempt to synthesize the latest developments in the fields of genetics, nutrition, and medicine and offer you practical tips and stories you can use in your own unique health journey. If you enjoyed this podcast, you can find more information online at mygenefood.com.

John O'Connor

John O'Connor is the founder of Gene Food, host of the Gene Food Podcast and a health coach trained at Duke's Integrative Medicine Program. Read his full bio here.

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