YT YouTube2Text

YouTube2Text → Transcripts → What REALLY Causes Glycation (Is Sugar Really the Problem?) (EB # 137)

What REALLY Causes Glycation (Is Sugar Really the Problem?) (EB # 137) — Transcript

by Jay Feldman Wellness · 10,760 words · 1,644 segments · language en · Watch on YouTube

Open in transcriber Summarize with AI Download SRT/VTT

Full transcript

0:00We're told that sugar is the primary
0:02driver of glycation, but that's not the
0:04full picture. And I'll explain why in
0:06today's episode of the Energy Balance
0:07podcast, a podcast where we explore
0:09health and nutrition from the
0:11Bioenergetic View and teach you how to
0:13maximize your cellular energy to
0:15maximize your health. In today's
0:16episode, I'll be going over why glucose
0:18and fructose are not the primary drivers
0:20of age formation. I'll also discuss
0:22whether blood sugar spikes cause
0:24glycation, how fats and ketones can
0:26cause glycation, what's really
0:28responsible for glycation that occurs in
0:30type 2 diabetes, and also whether
0:32fructose actually causes more glycation
0:34than glucose. As always, to check out
0:36these studies, articles, and anything
0:38else that I referenced throughout
0:39today's episode, you can head over to
0:41jfeldmanwellness.com/mpodcast.
0:43And with that, let's jump right in. All
0:46right. So, in the alternative health
0:47sphere, we have this general idea that
0:50sugar causes glycation, which then
0:52causes aging. It literally ages your
0:54cells. It ages your body and causes you
0:56to age and degenerate. And if you eat
0:59more carbohydrates, which all break down
1:01into sugar, then you'll have higher
1:03blood sugar levels and higher sugar
1:04availability in general, you'll have
1:06more blood sugar spikes, and this will
1:08cause more glycation. And then this is
1:10going to damage your blood vessels. It's
1:12going to damage all of your organs. And
1:14then it's going to age you. It's going
1:16to cause degenerative processes and
1:18cause, you know, chronic health issues.
1:20And you'll frequently hear things uh
1:23like that glucose and fructose spikes
1:25will cause glycation. So avoid high carb
1:27diets, avoid eating frequently as well.
1:30You know, uh having fewer meals is
1:31better because you have fewer of these
1:33spikes. We'll also hear that in general
1:35low carb diets will lead to lower blood
1:37sugar. So then they'll lead to lower
1:39glycation. So a low carb diet is better
1:41from a glycation standpoint. We'll hear
1:43that fructose is more glycating than
1:45glucose. Sometimes people will say as
1:46much as 10 times more glycating than
1:48glucose. So we should be avoiding
1:50fructose at all costs. Any sources of
1:52fructose, whether it's high fructose
1:54corn syrup in soda or it's fructose
1:57that's found in fruits. And then we'll
1:59also just hear in general that we want
2:00to cut out all sugar sources to prevent
2:02glycation. again with the idea that
2:04sugar sources also includes just any
2:06carbohydrate that you know will
2:08eventually break down into sugars into
2:10glucose and fructose or galactose. But
2:13uh in any case, this is the kind of
2:15general lay of the land that we're
2:16given. But we'll be talking today about
2:19why this is not the case. And this will
2:21be a two-part uh series here talking
2:23about glycation because there's a lot to
2:25dig into, a lot of misconceptions and
2:27misunderstandings when it comes to
2:29glycation. And so we want to make sure
2:30that we dispel all of that and and dig
2:33into the details here. And we'll start
2:35with just the question of what is
2:37glycation, what's going on here, and
2:39then we'll talk a bit about what causes
2:41it and what the process looks like. As a
2:43starting place, the kind of strict
2:44definition of glycation is basically the
2:46chemical modification of an amino acid
2:49by a sugar. And this is an interaction
2:51that then damages the amino acid. And
2:53typically that amino acid can be a part
2:55of a larger protein. And most of your
2:57body is made up of protein. So this can
2:58be you know a sugar interacting with
3:00some sort of protein structure uh that
3:03then damages it and as this degradation
3:06occurs it eventually leads to more
3:09advanced glycation products. There are
3:11early intermediate and advanced
3:13glycation products and so as this
3:14process goes on you tend to progress
3:17toward the advanced glycation end
3:18products. And so that's kind of the very
3:21strict definition. But it's also worth
3:23mentioning that glycation products, you
3:26know, everything up to the advanced
3:27glycation products are also produced
3:29without any sugar at all from fats,
3:32through lipid peroxidation. We'll talk
3:34about that also through ketones and
3:36through amino acids. So with that, the
3:38broader definition of glycation
3:40generally includes these things and
3:41basically involves any process that
3:45creates damaged amino acids that are
3:47then called glycation products. So
3:50that's really what we're talking about
3:51here is damage to amino acids, damage to
3:53proteins. And this can happen through a
3:56number of different mechanisms and from
3:57a number of different substrates, a
3:58number of different kind of precursors.
4:01And so the general progression that we
4:03have when it comes to glycation looks
4:07like this. So we start with the early
4:09glycated products. Then we have the
4:10intermediate glycated products and then
4:12the advanced glycated products or the
4:14advanced glycation end products. And
4:16what we're seeing here is the kind of
4:17standard diagram that you'll see that
4:19starts with a sugar. Normally this is
4:21going to be glucose. We'll talk about
4:23this with fructose as well. and then
4:24goes through its progression here into a
4:26shift base and then an amoddori product
4:28which then can become an advanced
4:30glycation end product. So that kind of
4:32top part here is normally in a lot of
4:35cases, especially in the low carb
4:36sphere, that's kind of the full picture
4:37that we're given. But there's a lot more
4:39to this picture that we want to discuss.
4:41And you can see a little bit at the
4:42bottom where you can see that
4:43intermediates from glycolysis,
4:45glycolytic intermediates can also become
4:47advanced glycation end products. On the
4:49bottom middle here, they show that lipid
4:51peroxidation can also cause advanced
4:53glycation end products. And we'll be
4:54talking about those things in detail,
4:56but this is just our kind of general uh
4:58framework. And then here are some
5:00examples that we have of advanced
5:02glycation end products. Some of these
5:04actually aren't advanced. Some of these
5:05are like intermediate glycation end
5:07products. You can see hemoglobin A1C.
5:09That's one that we measure in the blood.
5:10And so we'll definitely be talking about
5:12that. But a number of these other ones
5:14here. CML is going to be one that comes
5:15up quite a bit. And you can see the
5:17acronyms here for a number of different
5:19advanced glycation end products. Uh CEL
5:22is another very common one that we'll be
5:24discussing as well. It's one that's
5:25looked at in some studies. It's not
5:27important to know the details here, you
5:28know, as far as these different ages,
5:30but this is basically the product of
5:33glycation if it progresses on without uh
5:36something kind of preventing it or
5:38causing it to go in the other direction,
5:40which we'll talk about here in a moment.
5:42But it is worth noting that advanced
5:43glycation end products are not a good
5:45thing. They do have negative effects. Uh
5:48they are generally inflammatory. They're
5:50generally damaging and they actually
5:51damage the proteins.
5:53uh that renders them ineffective, unable
5:56to uh you know exert the processes that
5:59they need to for function. And so
6:01generally we don't want to see increased
6:03ages. And another thing that they do is
6:05they activate what's called the rage the
6:06receptor for advanced glycation end
6:08products R A G. And that then has a
6:11number of downstream effects. And so we
6:12can see that here where we have the ages
6:14and when they interact with rage you
6:15then see the activation of these
6:17different inflammatory pathways. In this
6:20case, we can see that they increase
6:21NFCappa beta, which is a an inflammatory
6:23cytoine. We can see that it leads to all
6:25these pro-inflammatory processes. And
6:28this can contribute to endothelial
6:29damage, kidney cell damage, liver
6:31disease, obesity, and on from there.
6:33It's generally not a good thing um in
6:35terms of its kind of causitive effects
6:37where it does drive inflammation and
6:39damage and also it's generally happening
6:41in the context of chronic health
6:44conditions and a highly inflammatory
6:46state and we'll talk about that too. But
6:48so that's our broad picture in terms of
6:50the progression of glycation and also
6:54you know what ages are and their kind of
6:55general effects. But it's worth talking
6:57about the details in terms of the
6:59sources of ages because as I've alluded
7:01to the general narrative we get is that
7:03glucose or fructose are glycating. Those
7:06are the main glycating agents and they
7:08cause the production of these advanced
7:10glycation end products. And so we might
7:12see something like this. Again, this is
7:14similar to that diagram I was showing
7:16you earlier where we're seeing the
7:17progression from glucose into the early
7:19intermediate and advanced glycation end
7:21products. And there's a a feature here,
7:25another aspect of this that's important
7:26to mention, which is the timeline
7:28through which this happens. This is
7:30actually an extremely slow process. And
7:32we can see this here. It's it's a little
7:35bit blurry, so it's kind of hard to see,
7:36but they show that that progression into
7:38the early glycation products that takes
7:40days to weeks. So this is again a very
7:43slow process. You have to have a lot of
7:44time for this interaction between the
7:46glucose and amino acids in this case.
7:49And then in the process of going from
7:50early glycation products to advanced
7:52glycation end products, we're talking
7:54about a time frame of months to years.
7:57So it's an extremely slow physiological
8:00process. And as we'll talk about, this
8:03isn't a permanent process until it
8:06reaches the advanced stage. So when you
8:08have the early and intermediate
8:09glycation products, these are reversible
8:12uh pathways. And so we can actually uh
8:15detoxify these early and intermediate
8:17glycation products. And so with how slow
8:19this happens, this is not particularly
8:22concerning relative to other things that
8:24are far more glycating. But this general
8:26glycation process of, you know,
8:28interaction between glucose and amino
8:29acid like this is a very very slow
8:32process. And it requires that you have
8:34this free sugar available and
8:36interacting with an amino acid for a
8:38pretty extended period of time. And
8:40again during this period of time there's
8:42a lot of time for detoxification to
8:44occur. And it's important to note if we
8:47look back at the uh first image here
8:50that the conversion from glucose to a
8:52shift base that's reversible. It can go
8:54back from a shift base back to glucose.
8:56And the conversion from a shift base to
8:58an amodori product is also reversible.
9:00So all the way up to these intermediate
9:02glycation end products, you can go
9:04backward and we'll talk about what will
9:06detoxify and also what will lead to the
9:08regression back toward uh glucose and
9:11basically prevent this from continuing
9:13on until it becomes the advanced
9:14glycation end products. Once that
9:16happens, it is permanent and that you
9:19can't go backward to the intermediate
9:20glycation products, but we can still
9:22clear out those advanced glycation end
9:24products. So we can still clear out the
9:26ages. And so we'll talk about that
9:28process as well and what affects it. So
9:31that's the glucose side. We'll talk a
9:33bit more about fructose later on. It's a
9:35very parallel process uh as far as what
9:38we saw here with glucose. But despite
9:41the name glycation, which does imply
9:43that this is glucose driven, it's not
9:46only driven by sugars. It's not only
9:48driven by glucose and fructose. And it
9:50can also be driven by fatty acids and
9:52ketones even in the complete absence of
9:55glucose or fructose. And so that's
9:57touched on here in this diagram where
9:58again we see the early glycation
10:00products, you know, the shift base
10:02amidori products from glucose. You know,
10:04we just talked through that process and
10:05how those can be converted over to the
10:06right into the advanced glycation end
10:08products. But you also see in the bottom
10:10left we have these oxoaldahhides
10:13and these are intermediate glycation
10:15products. They're also called
10:16dicarbonial or alpha dicarbonial. We'll
10:18be talking a bit about these because
10:20there's a number of different substrates
10:22that can be converted into these and
10:24these are really highly reactive. We'll
10:26talk about the details because it's
10:28crucial to get into the details with
10:30these. But these are really major
10:32drivers of the advanced glycation end
10:34products. Many many times more glycine
10:37than something like glucose. And as you
10:39can see in the bottom left here, lipids,
10:41amino acids, and ketone bodies can all
10:43be precursors to these alpha
10:46oxoaldahhides, these dicarbonial again
10:48we see here, glyioxil, methylioxyl, and
10:51glycoaldahhide. These are the three
10:52primary ones that you want to be aware
10:55of. And again, these can be produced and
10:58we'll go through the pathways uh
10:59briefly. We'll just kind of go through
11:00an overview of them in terms of how
11:02lipids, amino acids, and ketones can
11:04become these and then can become
11:06advanced glycation end products. again
11:08entirely in the absence of sugar. And
11:10that's very important because that's not
11:12normally the narrative we're given.
11:14We're given the narrative that this is
11:15sugar driven. This is glucose. This is
11:16fructose. And so we have a a good
11:18example here when it comes to looking at
11:21the age content, the advanced glycation
11:23end product in foods. And this is not
11:25something that we generally want to
11:26concern oursel with too much. The
11:28absorption of these uh ages is pretty
11:31low and there's very high levels of
11:32excretion. So I would say generally we
11:34don't have to be concerned about the
11:35amount of ages in food but looking at
11:38the age content of food illustrates how
11:42much advanced glycation end products we
11:44can have or how much glycation we can
11:46have even if we were eating a very low
11:48carbohydrate diet even without uh much
11:50if any carbohydrates available. And so
11:52we'll look at this table here. This is
11:54from a study titled advanced glycation
11:56end products ages formation chemistry
11:58classification receptors and diseases
12:01related to ages. And we can take a look
12:03at this table and we're looking at the
12:05age content per 100 grams. And looking
12:08at these numbers, it's pretty surprising
12:10because what you might expect is the
12:12sugar containing foods will have the
12:13highest amount of ages. You know,
12:15apples, um they show tomatoes, they show
12:18honey and um bread, which of course
12:22that's a starch, but you know, that
12:24starch will break down into glucose. And
12:25the amount of ages in these things is
12:27very small. um apples even when they're
12:29baked, you know, fresh apple, it shows
12:3013, but then with a baked apple, you
12:33would think with, you know, introducing
12:34heat into these free sugars, you would
12:36see a lot of age formation, and you
12:38don't. Only level 43. Uh honey at 7. And
12:42then when we compare that to some of the
12:45uh fat and carb sources, it's pretty
12:48surprising. So with butter, we see a
12:49level of 26,000. And again, I'm not
12:52saying that that's a bad thing. As I was
12:54mentioning, I'm not necessarily
12:55concerned about dietary age content
12:57here. And I think butter is is generally
12:59a health food, but it definitely says
13:01something when, you know, someone is
13:03trying to eat a, let's say, a
13:05butter-based diet, a highfat diet, a low
13:06carb diet to avoid ages. Well, obviously
13:09butter and the components in there are
13:11not immune to ages. We see that when we
13:13look at chicken as well. So, boiled
13:15chicken has a level of 957. Uh, chicken
13:18breast that's raw level is 769. beef
13:21that's raw 707. Uh obviously when it
13:24gets into the cooked meats here, you
13:25know, cooked turkey and bacon at bacon's
13:28at 91,000.
13:29Uh so again, this doesn't mean that we
13:32shouldn't be eating, you know, beef or
13:34chicken breast or something. That's not
13:35at all what I'm saying. But definitely
13:37says something about this idea that you
13:40know if if it's as simple as the sugar
13:42leads to age formation, age production,
13:44then you know we we wouldn't be seeing
13:46these sorts of values, these massive uh
13:49orders of magnitude differences between
13:51the age content of these different
13:52foods. Uh again, not something to be
13:54particularly concerned about from the
13:57dietary side, but as we'll continue to
14:00discuss as we go through some of the
14:01physiology here and then talk about the
14:03implication of different diets and you
14:06know what will affect these different
14:08pathways and how we can actually
14:09minimize glycation. You know, one thing
14:12that we're definitely getting at is that
14:13carbohydrates and sugars are not the
14:15culprits behind glycation. So, you don't
14:17need to avoid them for that reason. But
14:19that doesn't mean that all carbohydrates
14:20are created equal when it comes to our
14:22metabolic health. And the same goes for
14:24fats and proteins as well. They're not
14:25all created equal. And that's why I've
14:27created the energy balance food guide to
14:29help you determine exactly what to eat
14:30to optimally support your metabolism,
14:32and help you lose weight, improve your
14:33digestion, get amazing sleep, boost your
14:36energy, and so much more. The energy
14:38balance food guide is a one-page
14:39infographic that organizes foods on a
14:41spectrum based on how effectively they
14:42support your metabolism. And it also has
14:44a separate spectrum that adjusts this
14:46scale for you in the case that you're
14:47dealing with various digestive issues.
14:49The food guide makes it extremely easy
14:51to get started with a bioenergetic
14:52approach to optimizing your health. So
14:54head over to jfeldmanwellness.com/guide
14:57to download your free energy balance
14:59food guide. With that, let's talk a bit
15:01about those dicarbonals. We talked about
15:04these a little bit earlier. you know,
15:06glyioxil, methyl gllyioxil, and uh these
15:10are really the primary drivers of age
15:13formation. So, it's important to spend
15:15some time talking about these and what
15:17their sources are and how we can
15:18minimize their production and again
15:20whether it all just comes back to sugar.
15:22And I do want to mention here Chris
15:24Master John has a really good article on
15:26this titled Where do most ages come
15:28from? Oh, glycation, how thy name hast
15:31deceived me. It's a great title for the
15:33article as well. And so I just wanted to
15:36mention that here because he discusses a
15:38lot in terms of these dicarbonial and uh
15:41so a lot of the information here is
15:43building upon uh his article. So I did
15:45just want to mention that is one that I
15:47would highly recommend checking out. But
15:49with that in mind, let's talk about what
15:52these dicarbonials are, how they're
15:53produced, what they do, and and why
15:55they're so concerning. The first to
15:57mention here, so basically there are
15:59three dicarbonial that are generally
16:01considered to be the glycating
16:02dicarbonial. the ones that are going to
16:04create the advanced glycation end
16:06products and they themselves are
16:07considered intermediate glycation
16:09products and these are methyl glyioxil
16:11glyioxil and three deoxylucone
16:14and again it's not you know the names
16:16aren't particularly important I wouldn't
16:17concern myself too much with those but
16:19we see those here and we can also see
16:21their different sources here so we
16:23talked about the malard reaction this is
16:25the you know glucose into the shift
16:27bases the amdoori products and we talked
16:29about those as a potential source of
16:30these and ages but there are a handful
16:33of other factors as well like lipid
16:34peroxidation, glycolysis, and we'll talk
16:37about uh some other ones here too. You
16:39know, they mentioned the polyal pathway.
16:41There's a number of different pathways
16:42that can lead in here and we're going to
16:43talk about them in a little bit more
16:45detail, not a ton, but uh it's really
16:48important to talk about these
16:49dicarbonial because they are the primary
16:51precursors to the ages. And we can see
16:54some of these ages here that we saw in
16:55that chart earlier. And the reason for
16:57this is because dicarbonals are 20,000
17:00times as reactive as glucose. And so
17:03someone is describing that glucose is
17:05this compound to be very fearful of
17:07because it's so glycating. Well, you
17:10definitely want to keep that in context
17:11when we're talking about compounds here
17:13that are 20,000 times as reactive and
17:15that we want to be much more aware of
17:18and aware of what actually increases
17:19their formation, which does happen to
17:21include other substrates like fats and
17:23and ketones as we'll discuss. But just
17:26going to share this quote here first uh
17:28describing how glycating they are. And
17:30so this is uh from a study titled
17:32dicarbonial intermediates in the malard
17:34reaction. And they state the formation
17:35of alpha oxoaldahhides this is the
17:38dicarbonial that we're talking about
17:39here enhances and redirects glycating
17:42activity in the malard reaction since
17:43alpha oxoaldahhides are up to 20,000fold
17:46more reactive than glucose and glycation
17:48processes and are predominantly arginine
17:50direct to glycating agents. So, uh, just
17:53pointing out just highlighting how, uh,
17:56concerning these dicarbonials are when
17:58it comes to glycation. And one of the
18:00main ones here that we've mentioned a
18:01couple times is methylioxil. This is one
18:03of the most common ones that's measured
18:05in different studies and that's looked
18:06at in general. So, we're going to talk a
18:08little bit about methylioxil and what
18:10kinds of things form it and what, you
18:12know, what the contexts are for
18:13methylioxil. We're going to start here
18:15by looking at one of the primary sources
18:17of methylioxil, which is the trios
18:19phosphates. So uh again I know this
18:23sounds a little complicated but you know
18:24as we go through the physiology here
18:26we'll get into more application as well
18:28and also if you you know I'll I'll try
18:31to simplify it here but um you know some
18:33of the big names and everything sound a
18:35little bit more technical than they are.
18:37So what we're talking about here is when
18:39we have glucose on the left and we start
18:41to run through glycolysis which is the
18:43process of converting glucose to energy
18:45uh we produce these different steps
18:47along the way these different
18:48intermediates and a few of them are what
18:49are called trios phosphates and one of
18:52these is glyceraldahhide 3 phosphate and
18:54then the other one is dihydroxy acetone
18:56phosphate that's the DHAP so those two
18:58are just produced anytime you're
18:59converting glucose into energy and well
19:02we'll talk about the context of of this
19:04but essentially if there's a buildup of
19:06these intermediates It's because glucose
19:07metabolism is blocked. You'll see them
19:09build up. And when that happens or just
19:12if there's, you know, an excessive
19:13amount, we'll talk about those contexts.
19:15You'll see a conversion into
19:16methylioxil. Both of these can be
19:18precursors to methylioxil. And again,
19:20methyl gyioxil being one of these
19:22dicarbonial that's very very glycating,
19:24one of the main glycating agents. And we
19:26can see if we follow that methylioxil
19:28arrow to the right, we can see that it
19:29produces the ages. Now we can also see
19:32in this diagram another source of
19:33methylioxil which is the polyunsaturated
19:35fats uh that become lipid peroxides. So
19:39this is something we talk about all the
19:40time. We talk about the negative effects
19:42of PUFA and that's because they can get
19:44damaged. Um they're inefficient for
19:46energy production and they produce these
19:47lipid peroxides. And one of the negative
19:49effects of these lipid peroxides is they
19:51can directly be converted into
19:53methylioxil which again can then become
19:55ages. We'll also talk about some ways
19:57that lipid peroxides can also just
19:59directly become ages or advanced lip
20:01oxidation end products. We'll talk about
20:03those in a bit and you can kind of see
20:04that on the right of this diagram here.
20:06But the important point being that you
20:07know these are two different sources. We
20:09have these triosphosphates coming in
20:11this case from glucose. They could also
20:12come from fructose uh or they could come
20:14from gluconioenesis or they could come
20:16from other sources. We we'll get into
20:18all that. But then also we have the
20:20polyunsaturated fats on the right that
20:22can produce this methylioxil. And you
20:24can also see on the bottom here that
20:25methylioxil can be converted or
20:27basically detoxified and converted into
20:29deactate. This is via gioxilase and
20:32utilizes glutathione. And this is
20:34actually something that we'll be talking
20:35about more in part two. But those are a
20:37couple sources here of methyllyio.
20:39Couple of others include uh one the
20:41amino acid thrienine and then acetonein.
20:44So we see that described here where
20:45they're showing the different uh sources
20:47of methylioxyl glycolysis and lipid
20:49peroxidation that we discussed but also
20:51thrienine which is an amino acid and
20:54acetone which we'll kind of show that
20:56pathway in a moment but these are both
20:58also potential precursors to methodox
21:01and then we're going to see this you
21:02know we see this pathway here when it
21:04comes to acetone and uh you know this is
21:08pretty important because acetone is one
21:10of the main ketones that's produced and
21:12it's a direct precursor to methylioxil
21:15and then from this pathway it can
21:17actually be converted into glucose in
21:19the process of gluconogenesis. So one of
21:21acetone's main roles. So if if someone's
21:23on a ketogenic diet and they're
21:25producing a lot of acetone, one of the
21:26main things that happens with that
21:27acetone is it's used for gluconogenesis.
21:30It gets converted into glucose. In that
21:32process, methylioxil has to be produced.
21:35And so you end up with this these
21:36increased levels of methyoxil and a
21:38direct increase in ages. And we'll be
21:40talking about this a bit more later on,
21:42but it's uh pretty important to note
21:44here and we just see this pathway drawn
21:45out uh here in this diagram. And then
21:49with that, something else that we want
21:50to be aware of on a low carb diet or a
21:52diet when we're eating excessive amounts
21:54of protein, additional lack of carbs or
21:56especially on a ketogenic diet as well
21:58is gluconneogenesis. And this is also
22:00something that comes into play with
22:01insulin resistance and diabetes. And so
22:04we see this here where if we look at a
22:06on the left we saw uh you know those
22:08trios phosphates which are in the middle
22:10there. Glucose can be a source of those.
22:12But another source of those is
22:14gluconogenesis which we see that pathway
22:16all the way on the left the pink and
22:18yellow there where uh anytime we're
22:20producing glucose from any substrate we
22:22will see these triosphosphates that have
22:25to be produced along the way and those
22:27are also precursors to methylioxil. So
22:29if you think that you're avoiding any of
22:31these pathways by avoiding
22:32carbohydrates, this obviously is is not
22:34the case and we're still um going
22:36through all these intermediates that are
22:37the precursors to methylioxyl and to
22:40ages. And then we see on the right here
22:42just a few of those other sources. You
22:44know, we see acetone on the bottom right
22:46and accetoacetate as a precursor there
22:48and um you know the malard reaction and
22:51thrienine that we had talked about
22:52earlier. And so these are main sources
22:54of methylioxil which is one of the main
22:56drivers of age formation. Obviously,
22:58what we're seeing here is this is not
23:00just a sugar problem. There's a bunch of
23:02different substrates that can lead to an
23:03increase in methylioxil. And we'll talk
23:06about the context under which this
23:08happens and how to prevent it from
23:09happening. But, you know, it's
23:11definitely clear here uh that this is
23:13not just a sugar-driven process. And
23:15this study goes along with this as well
23:17and basically shows us how in healthy
23:19conditions when we're utilizing glucose
23:20as a fuel, when we're utilizing
23:22carbohydrates as a fuel, methyl glyioxil
23:24production is actually pretty minimal.
23:26Uh but of course when we're not under
23:28healthy conditions that's when things
23:29can change. But we'll take a look at at
23:31the quote from this study titled
23:32methoglycal induced dicarbonial stress
23:35in aging and disease first steps toward
23:37glyioxilase 1based treatments. And they
23:39state methylioxil is formed mainly from
23:42the spontaneous trace level 0.05 to.1%
23:46flux degradation of triosphosphates.
23:49This increases with increased
23:50triosphosphate concentration and
23:52anorobic glycolysis. So just to pause
23:54here under normal uh conditions we're
23:58seeing a very very tiny amount of methyl
24:00gllyio production but they mentioned
24:03that this increases in anorobic
24:05glycolysis. This is something that we
24:07see going on when glucose metabolism is
24:09inhibited when there's excess fatty acid
24:10metabolism going on. This is something
24:12we've talked about in prior episodes on
24:14insulin resistance. I'll link to those
24:15in the show notes. Moving along here,
24:17they state abnormal physiological
24:19metabolism leading to increased
24:21triosphosphate concentrations are
24:23increased glucose metabolism and
24:25hypoglycemia associated with diabetes.
24:27This isn't really increased glucose
24:29metabolism per se. It's increased
24:30glycolysis or anorobic glycolysis as
24:32they mentioned with inhibited glucose
24:35oxidation. Uh so basically you have kind
24:37of like a broken glucose metabolism and
24:39this is a case where you'll see
24:40increased triosphosphates which then
24:42will increase methylioxil. They go on to
24:44state another situation which is
24:47impaired disposal of glyceraldahhide 3
24:49phosphate by the decreased activity of
24:51the reductive pentosphosphate pathway
24:53and increased dependence on anorobic
24:54glycolysis and related increased
24:56metabolic flux in hypoxia which is the
24:59pasture effect that may also arise from
25:01other metabolic pathways where
25:03triosphosphates are intermediates
25:04including gluconogenesis
25:06glyceroneogenesis and rare
25:08triosphosphate isomease deficiency. So
25:10that last part is important here as
25:12well. When we're seeing increased
25:13gluconogenesis, these intermediates will
25:15also be elevated and that's going to
25:16happen in situations like insulin
25:18resistance and type 2 diabetes due to
25:20high stress hormones and also under the
25:22case of low carb diets, we see increased
25:24gluconneogenesis as well. So that's just
25:26a little bit of context regarding
25:27methoglyio production under normal
25:29states versus these uh impaired
25:31metabolic states. And that brings us to
25:34one of the other main sources here that
25:36we want to talk about which is the
25:37peroxidized fats. the proxidize
25:39especially polyunsaturated fats since
25:41those are the ones that are particularly
25:44uh susceptible to damage and and to
25:47peroxidation and we see that in this
25:49diagram here we talked about this one
25:50earlier where we can see that the
25:52polyunsaturated fats that get uh become
25:54the lipid peroxides if we follow down to
25:56the right we can see the production of
25:58malan dialhide and four hydroxy nonenol
26:01that's also 4 HNE there's some other
26:03ones in here there's some other
26:04compounds that fall in this category
26:06like acroon as well these are aldahhides
26:08that are produced from lipid
26:10peroxidation. They're implicated in
26:11basically every chronic health condition
26:13you can think of and they're also
26:15precursors here to the advanced
26:16glycation end products and also to
26:19methyl glyioxil. They can also be
26:20converted to these dicarbonial which
26:22they aren't actually showing that direct
26:23arrow here but that is also a potential
26:26pathway. And so this is extremely
26:28important. The polyunsaturated fats are
26:29huge drivers of advanced glycation end
26:32products that we want to be aware of.
26:34And this is especially notable when you
26:36have figures, some of the figures who
26:38are most prominently fear-mongering
26:41about sugars because of glycation.
26:43Figures like Ken Barry who have stated
26:47in the past that naturally occurring
26:49omega sixes aren't harmful. Yet, what we
26:52see here is that they're actually direct
26:54precursors to advanced glycation end
26:56products and they're actually far more
26:57glycating than sugars like glucose. And
27:00we see that here. This is a study
27:03looking at omega 6s and their propensity
27:05toward uh forming advanced glycation end
27:08products. This is a study titled the
27:09advanced glycation end product nepsilon
27:12caroxymethylsine is a product of both
27:14lipidroxation and gly oxidation
27:16reactions and they state CML was also
27:19formed in a time dependent manner in RNA
27:22incubated under aerobic conditions in
27:24phosphate buffer containing arachidonate
27:26or lenolate. So lenolate that's linoleic
27:29acid that's the omega6 fat that's you
27:31know really common in the high omega6
27:33foods. They state only trace amounts of
27:35CML were formed from olate. After 6 days
27:37of incubation the yield of CML and RNAs
27:40from arachidonate was about.7 millles
27:42per mole of lysine compared with only 03
27:45millles per mole of lysine for protein
27:47incubated under the same conditions with
27:49glucose. Gioxil a known precursor CML
27:52was also formed during incubation of
27:54RNAs with arachidonate. So arachidonic
27:57acid is a downstream fatty acid that
28:00gets produced from linoleic acid. It's
28:01produced from the omega 6s. And what we
28:04see here is a 23 times difference
28:06between arachidonic acid and glucose in
28:09terms of forming advanced glycation end
28:11products. And they did actually look at
28:12leninoleic acid as well. And they found
28:14it to be about 10 times greater than the
28:18glucose formation of advanced glycation
28:20end products. The amount was about 35
28:23millles per mole of lysine. So what they
28:25found was that the omega 6s were 10
28:27times more glycating than glucose. And
28:30it's worth noting this is only
28:31considering the advanced glycation
28:33product CML that's produced from the
28:35omega 6s. It's not considering the alle
28:38the advanced lip oxidation end products.
28:40And if we account for those as well then
28:42you know we would really see that the
28:44polyunsaturated fats and especially
28:45omega sixs are far more concerning from
28:47this standpoint. And the alles this is
28:51basically an alternative way. It's it's
28:54independent generally from the advanced
28:55glycation end products. Uh they fall
28:57under the same umbrella. They have the
28:59same effects. They actually uh do the
29:01same things in terms of damaging the
29:03proteins. Uh you know accumulating with
29:05time in these chronic health conditions
29:07and degenerated states. Um they activate
29:09the same rage receptor the receptor for
29:11advanced glycation end products. It's
29:13also activated by these ALES and it
29:16activates the same inflammatory pathway.
29:17So they function you know basically the
29:19same uh but they're just being driven
29:22only from fats and from lipid
29:23proxidation. Basically what can happen
29:25and we can see this here in this diagram
29:26is that these aldahhides that are
29:28produced from the lipid proxidation the
29:31uh we see them here as reactive
29:32carbonial species this is the four hn
29:35mga chroen these can be converted into
29:39the dicarbonial like methyl gioxil and
29:41then can form you know the ages or as
29:44we're seeing here they can directly
29:46interact with the amino acids. So
29:47without needing to convert to
29:48methylioxil and then convert to ages
29:51these aldahhides can directly interact
29:53with amino acids and form what are
29:55called als these advanced lip oxidation
29:58end products which again are just as
30:00harmful as the ages. And we see this
30:04here in this other uh diagram where we
30:06see uh they're highlighting specifically
30:09the the PUFA the lipids and all of the
30:12um products that they produce here these
30:14reactive carbonals and then how they can
30:16end up creating ages and ales. So it's
30:19really a huge part of the picture here
30:21that isn't often talked about is the
30:23polyunsaturated fats and how much of a
30:26driver they are of uh ages and alles and
30:31uh when it comes to this broader
30:32conversation of of glycation they're you
30:34know really important player. So we have
30:36this general landscape which is
30:38basically that in an impaired metabolic
30:40state we'll see increased precursors to
30:44advanced glycation end products. We'll
30:46see increased production of these
30:47advanced glycation end products. This
30:48comes from all sorts of sources, whether
30:50it's sugars, fatty acids, or ketones.
30:54And avoiding any of these on their own
30:56is is not going to be a solution, right?
30:58That's not actually uh going to make a
31:01difference when it comes to age
31:02formation. We really need to be looking
31:04at the metabolic state. But it's worth
31:06addressing, I think more specifically,
31:08the concerns regarding blood sugar and
31:11glycation because again, we're
31:13constantly bombarded with this idea that
31:15a glucose or a fructose spike after
31:17eating carbohydrates will be causing
31:19glycation, damaging blood vessels, and
31:21causing degeneration. And so, let's
31:23let's dig into that question a little
31:24bit of whether high blood sugar does
31:26actually cause glycation and advanced
31:29glycation end products. The first thing
31:30that's really worth noting here is that
31:33what's going on in the blood in terms of
31:35glycation is far less important because
31:38most of the formation of glycation
31:40products is occurring inside the
31:41tissues. It's not going on in the blood.
31:44So these short-term fluctuations of
31:46sugars or fatty acids in the blood are
31:49not as concerning versus the metabolic
31:52state of the tissues. And this study
31:54describes that here. This is a study
31:56titled quantitative screening of
31:57advanced glycation end products and
31:59cellular and extracellular proteins by
32:01tandem mass spectrometry and they state
32:04quantitative screening showed high
32:05levels of advanced glycation end
32:07products and cellular protein and
32:08moderate levels in protein of blood
32:10plasma. Low levels of free advanced
32:12glycation end products were found in the
32:14blood plasma and levels were 10 to
32:15100fold higher in the urine. This is
32:17when they're being excreted. We show for
32:20the first time that cellular proteins
32:21are more highly glycated than
32:23extracellular proteins. So, and they
32:26they go through this in the study with
32:27different tables, but what they're
32:28essentially finding is that there's
32:30relatively low amounts of the glycation
32:32products in the blood and outside of the
32:35cells. Most of this is happening inside
32:37the cells, inside the tissues. And so,
32:38what we really want to do is focus on
32:40what causes that, what affects those
32:42processes. One piece I want to touch on
32:45here that I think is important because
32:46there's a bit of conflation here is what
32:48goes on in type two diabetes. Because we
32:50know in type two diabetes that there's
32:52high levels of blood sugar and we also
32:53know in type two diabetes that there's a
32:56large amount of glycation that goes on.
32:59But what we're seeing in this state when
33:01people are connecting those two together
33:02and saying okay well blood sugar is
33:04causing the glycation is basically a
33:06huge conflation of these two factors.
33:08And it's the same thing that happens
33:10when we see high blood sugar and insulin
33:12resistance where the blood sugar is not
33:14causing the insulin resistance. It's the
33:16effect of the insulin resistance. It's
33:18the part of the body's response to the
33:20insulin resistance. It's not actually
33:21driving it. And same goes for insulin.
33:23Again, we've talked about this in those
33:25previous episodes on insulin resistance.
33:28But so we're seeing a similar situation
33:30here where the glycation that's going on
33:32here in type 2 diabetes is definitely
33:34related to the blood sugar, but it's not
33:37directly caused by it. it's actually a
33:39situation where it's being driven by the
33:41underlying metabolic state that's also
33:43causing the high blood sugar. And with
33:44that, we want to remember that the
33:46advanced glycation end products from
33:47sugars themselves is extremely slow.
33:50Right? We're talking days, weeks,
33:52months, years. And so, this is really
33:54not the primary source of glycation that
33:56we want to be concerned with. rather we
33:58do actually want to be concerned about
34:00glycation going on in the state but it's
34:02more so due to the poor glucose
34:03metabolism that's going on and the
34:05impaired metabolic state that leads to a
34:07low NAD+ to NADH ratio as well as the
34:09increased lipid metabolism and the
34:11increased gluconioenesis
34:13and that is what leads to the state of
34:15increased glycation because in this
34:17situation we kind of touched on this
34:19earlier we have a buildup of the
34:20glycolytic intermediates those
34:22triosphosphates that we talked about
34:24where basically the glucose isn't able
34:26to be completely metabolized and
34:27converted to ATP. It gets stuck and you
34:30have this buildup of intermediates. And
34:32they talk a bit about this in this study
34:34which is titled uh prevention of
34:36incipient diabetic nephropathy by
34:38highdoseseamine and benotamine. And they
34:40state supporting studies of messenal and
34:42endothelial cells in hypoglycemic
34:44culture have exemplified the key
34:46features of biochemical dysfunction in
34:48hypoglycemia. The accumulation of trios
34:51phosphates, increased denovo synthesis
34:53of dasogglycerol and activation of
34:55protein kinase C beta, oxidative stress
34:57linked to mitochondrial dysfunction
34:59sustained by high glycerero phosphate
35:00shuttle activity, concominant activation
35:02of the hexosamine pathway and the
35:04accumulation of methylioxil with
35:06increased formation of ages, increased
35:08concentrations of triosphosphate,
35:10glycolytic intermediates,
35:11glyceraldahhide 3 phosphate and
35:12dihydroxy acetone phosphate is the
35:15trigger for these processes. So I know
35:16that was a lot there. The important part
35:19being you know if we're kind of
35:20simplifying here the buildup of those
35:22trios phosphates which you know we went
35:24over that diagram before and we'll we'll
35:25go back to a similar one is really
35:27what's responsible and uh for the
35:29glycation in this state and this is the
35:31result of mitochondrial dysfunction
35:33basically impaired glucose metabolism
35:35and this is important because what we're
35:37seeing here is even in the condition
35:39with the highest blood sugar levels it's
35:41not the sugar in the blood that's
35:43responsible for the glycation. So this
35:45is really saying something when we're
35:46looking at a study like this. And so
35:48here's a diagram of showing the
35:51conversion of glucose to pyuvate. This
35:52is glycolysis. And we have those
35:54triosphosphates in the middle, the
35:56glyceraldahhide 3 phosphate and the
35:57dihydroxy acetone phosphate. These are
35:59the two that are precursors to methodio.
36:02And part of what's important here, you
36:03can see that the step after that
36:05converts the glyceraldahhide 3 phosphate
36:07to the 13 bif phosphoglycerate. This is
36:09just again, I know the name sound
36:11complicated, but we're just converting
36:12that glucose to energy. And this is one
36:14of those important steps. You can see in
36:17yellow, this requires NAD+ to be
36:19converted to NADH. And when we have a
36:21low NAD+ to NADH ratio, which happens in
36:24its own resistance, metabolic syndrome,
36:26interference in mitochondrial function,
36:28we're going to have interference in this
36:29step. It's not going to function as
36:30well. And we'll see this buildup of
36:33these triosphosphates as a result. And
36:36so this is part of why when we talk
36:38about that NADH ratio, you know, it's
36:40it's very important. This is not the
36:42only step that it's involved in, but
36:44this is something that we see happening
36:45in these states. We see this impaired
36:48glucose metabolism that leads to this
36:50buildup of triosphosphates which lead to
36:52advanced glycation end products. And we
36:55see this diagram as well. This is
36:56specifically, you know, we looked at uh
36:58the full one earlier. This is just a
37:00portion of of that one that we looked
37:02at. And this is from a paper
37:03specifically talking about the increase
37:05in these triosphosphates and glycation
37:08in disease processes like type two
37:10diabetes. And what we see here is these
37:12different sources. Uh the glucose that
37:15again is not going to be converted all
37:16the way down to pyuvate and then go
37:18through you know mitochondrial
37:19respiration it gets blocked and then
37:21also the gluconogenesis which is
37:22actually increased in the case of
37:24insulin resistance due to chronically
37:25high stress hormones. Again this is
37:27something we talked about in the insulin
37:29resistance series. But these are the
37:32sources of glycation in this uh
37:35situation. It's not just the glucose
37:36itself that's sitting in the blood. And
37:38the reason why this is so important to
37:40delineate is because it means that the
37:41moderate blood sugar bump that you get
37:43after eating even a high carb meal isn't
37:46actually responsible for glycation. It's
37:48not actually responsible for age
37:50formation. And we're seeing this in the
37:51most obvious situation of type 2
37:53diabetes where there's massively high
37:55blood sugar levels. And again, what we
37:57are seeing is that if we can't use
37:58carbohydrates effectively, that's when
38:00we start to see glycation to be a
38:02concern. And it's not just because of
38:04the carbohydrates that we're consuming
38:05at that point. It has to do with often
38:07times polyunsaturated fats that are
38:09implicated in that scenario. Has to do
38:11with gluconioenesis going on a stress
38:13hormones and a number of other things
38:14that are blocking uh mitochondrial
38:16respiration. And then that brings us to
38:18another uh point here that does go on in
38:21type 2 diabetes which is that there's
38:23elevated oxidative stress in this
38:25situation which causes the increased
38:26lipid peroxidation. We talked about this
38:28earlier because the lipid peroxides can
38:30be converted into the advanced glycation
38:31end products. But the other thing that
38:33it does is it reduces the clearance and
38:35detoxification of the intermediate
38:38glycation products and the advanced
38:39glycation products. So both sides of the
38:42equation are impacted in this impaired
38:45metabolic state. We see increased
38:47production and reduced clearance. But
38:49we'll discuss the clearance and
38:50detoxification side more in part two.
38:52That brings us to one of the other
38:55important misconceptions to discuss here
38:58and that has to do with fructose and
39:00glycation.
39:01So, we're often told again from the
39:04people who tend to fearonger regarding
39:06glycation and carbohydrates, we're told
39:08that fructose is more glycating than
39:10glucose. And if you're eating a lot of
39:12fructose containing foods, whether it's
39:14table sugar or fruit or uh soda or candy
39:18or whatever it is, you're going to see
39:19an increase in fructose and therefore an
39:21increase in glycation from fructose or
39:24what's sometimes called fruation. Let's
39:26talk about that a little bit. Again,
39:28there it's one of those situations like
39:29most where there's a kernel of truth in
39:31there, but the application of it and the
39:34way that it's often described is really
39:37totally irrelevant and it definitely
39:40does not mean that we need to be
39:41avoiding fructose in our diet. So, we'll
39:44look at here is a graphic of what's
39:46called fruation. And so, you know, we
39:49talked about the first pathway, pathway
39:51A, that's coming from glucose and that
39:53conversion down from glucose into ages.
39:55Pathway B is the same thing coming from
39:57fructose. And so it follows that same
39:59path. There are some other pathways of
40:01uh age formation from fructose, but this
40:03is kind of the the primary one. There's
40:05one called the wolf pathway and there
40:07there are some others. But uh in any
40:09case, much like glucose, we have this
40:11kind of basic pathway for the production
40:13of ages from fructose. And this is
40:16through a process that's basically
40:17equivalent. It's called fation. And so
40:20one thing that you might hear is that
40:21this futation process uh or or the
40:25capacity for fructose to cause glycation
40:27is uh far greater than with glucose.
40:30We'll often hear something along the
40:31lines of you know fructose is 7 to 10
40:33times more glycating than glucose. And
40:36there is an old study from around 1980
40:38that does look at this. They basically
40:39looked at fructose versus glucose and
40:42the reactivity of each uh in vitro. So
40:45this wasn't looking at it, you know, in
40:46a person who's consuming glucose or
40:48consuming fructose or anything like
40:49that, just looking at the reactivity
40:51between glucose and fructose. And in
40:53this case, they were looking at
40:54hemoglobin. And they did find that
40:56fructose's reactivity with hemoglobin
40:58was 7 1/2 times that of glucose in
41:02regard to forming shift bases. Remember
41:03that's that first step here of the
41:05fation. So it's suggesting that the
41:07fructose is about 7 and 1/2 times more
41:09glycating than fructose. And it's worth
41:11noting as I was kind of alluding to that
41:13this is only shown in vitro. And when it
41:15comes to the invivo studies, uh they
41:18don't actually show this comparison. And
41:19honestly, there's not a lot of great
41:21research looking at age formation in
41:24vivo. It's u just I guess you could say
41:26underststudied. Uh and you know,
41:28comparing different diets and and their
41:31impact on glycation and things like that
41:32is is just not commonly done. Uh there
41:35are studies looking at the impact of
41:38fructose on glycation in rodent models.
41:41We'll touch on that in a little bit and
41:43how relevant it is. But again, what a
41:45lot of these claims are based on when
41:46they're talking about fructose being 7
41:48to 10 times more glycine than glucose is
41:51this in vitro study. uh and even if we
41:54were to assume that this in vitro data
41:56is 100% applicable to humans in vivo to
42:00us in our kind of regular environment
42:01when we're you know eating a fructose
42:03containing diet. There are still some
42:07important caveats here that really
42:09nullify any relevance of this finding.
42:13And the first is that fructose levels in
42:15the blood are about 200 times less than
42:18glucose at baseline. So if we're
42:21concerned about let's call it eight
42:22times uh you know fructose is eight
42:25times more glycating than glucose. Well
42:26fructose levels in the blood at baseline
42:28are 200 times less than glucose. So that
42:31you know wouldn't be concerning if uh
42:33you know if we're not concerned about
42:35regular levels of glucose in a healthy
42:37metabolic state. We want to be concerned
42:38about that with fructose. And when it
42:40comes to the consumption of fructose,
42:43even when consuming massive amounts of
42:46fructose, the levels in the blood still
42:48are many, many times lower than glucose.
42:51So, we already talked about earlier why
42:53fructose or glucose in the blood is not
42:55a concern when it comes to ages because
42:56that's not where most glycation's
42:58happening and it's not just sitting
42:59there. But then on top of that, the
43:01levels in the blood, even if you're
43:03concerned about fructose being more
43:04glycating than glucose, the levels are
43:06so much less that it's not relevant.
43:09We'll look at some studies here that are
43:11uh describing that. And again, these are
43:13going to be looking at, you know, a
43:14level of fructose consumption of like 75
43:16grams all at once. That's, you know, the
43:19equivalent of consuming a few sodas at
43:20once. You know, this is not relevant to
43:23consuming a regular moderate or high
43:26carb diet from whole foods. So, we'll
43:28get into that here with this first
43:30study, which is titled metabolic aspects
43:32of fructose metabolism and metabolic
43:33disease. And here we just have a a quote
43:36talking about fasting concentrations of
43:38glucose and fructose where they state
43:40whereas normal fasting glucose
43:41concentrations in peripheral blood are
43:44around 5 millmer fructose circulates at
43:46less than 0.02
43:49millmer in fasted conditions. So 0.02
43:52millmer of fructose we're looking at
43:53about.36
43:55millig per deciliter. And if we're
43:57thinking, you know, fasting glucose of
43:5980 milligrams per deciliter, this is 222
44:02times lower at baseline, you know, at
44:05fasting. So so much less that again,
44:07even if fructose was 100 times more
44:10glycating than glucose, it would still
44:12be less concerning than fasting glucose
44:14levels of 80 milligs per deciliter,
44:16which obviously whether you're on a low
44:18carb diet or high carb diet, you know,
44:20you're not going to see fasting glucose
44:21levels that far below uh 80, especially
44:24in, you know, if you're insulin
44:26sensitive. So, uh, you know, in either
44:28case, it really wouldn't be relevant
44:30here. And then in this study, we'll look
44:32at what happens when you consume large
44:33amounts of fructose and what it it does
44:36to blood levels of fructose. So, this is
44:37a study titled effects of several simple
44:40sugars on serum glucose and serum
44:42fructose levels in normal and diabetic
44:44subjects. Again, this is looking at
44:45people who are metabolically healthy and
44:47people who have type two diabetes and
44:49what happens to fructose in the blood
44:51when consuming large amounts of
44:53fructose. And they were using 75 gram.
44:55This is the amount of fructose that's in
44:57around 3 and 1/2 cans of soda. So huge
45:00amount of fructose. And so we see here
45:02in figure three the levels of fructose
45:04after consuming 75 g. Uh and then we
45:07also see the level of fructose after
45:09consuming 75 g of sucrose and glucose.
45:11And so what we see after this massive
45:13intake of fructose is that the levels
45:15peaked at less than 7 milligrams per
45:17deciliter. So even if you're on a low
45:21carb or ketogenic diet and you're seeing
45:22a fasting blood glucose level of 80
45:24milligrams per deciliter, which by the
45:26way, most of what I see on uh from
45:28people who have been on longer term low
45:30carb diets is that that blood sugar
45:32level increases quite a bit. You know,
45:33often above 100 milligrams per deciliter
45:36with time of all the stress. But that
45:38aside, the less than 7 milligs per
45:40deciliter is still more than 10 times
45:42less than baseline levels of blood
45:44glucose. So even if fructose was 10
45:47times more glycating than glucose in
45:48vivo in a human, it still would be less
45:51concerning here than just fasting blood
45:53glucose levels. So uh what this really
45:56points to is is that fructose is uh not
46:00a concern when it comes to glycation in
46:02terms of blood levels, which is often
46:03what's being pointed to. And you would
46:05think, okay, well, in someone who's uh
46:08dealing with metabolic issues, who's
46:09insulin resistant, who has type two
46:11diabetes, maybe those blood fructose
46:13levels go way high, just like the blood
46:14sugar levels do. That's not actually
46:16what was found here. So, in figure five,
46:18they show normal subjects versus
46:19diabetic subjects. Any increase in serum
46:21fructose between the two was uh barely
46:24any different. And you can see the peak
46:26is still below 7 milligs per deciliter.
46:29So, uh the fructose levels in the blood
46:31are really not concerning. This is even
46:33after consuming 75 grams of pure
46:36fructose which by the way uh you would
46:39never get pure fructose in any foods.
46:41It's always paired with some amount of
46:43glucose whether we're talking honeyhe
46:44fruit table sugar which is 50/50 you
46:47know high fructose corn syrup which is
46:4855% fructose 45% glucose. Uh so even in
46:52this case of 75 grams of pure fructose
46:54which is essentially irrelevant to what
46:56a normal human would be consuming even
46:58then the fructose levels in the blood
47:00are not high enough to a point where it
47:01would warrant any concern in terms of
47:04fation. One of the next things that we
47:06often hear when it comes to this idea
47:08that fructose glycation or fruation is
47:11particularly harmful and we're getting
47:13this kind of fear-mongering spiel is
47:16that you can't measure fruation. So this
47:18could be happening in the background and
47:20you can never know if futation is
47:22actually going on and so it's this
47:24secret uh you know killer in the
47:27background that's going to slowly age
47:28you and again there's a negative truth
47:31in here which is that when it comes to
47:33the typical blood markers that are
47:34measured like hemoglobin A1C or
47:36fructosamine these are looking at early
47:39glycation products they're not looking
47:40at fruation products so it's true that
47:43in typical markers if you just look at
47:45A1C it's not telling you about
47:47hemoglobin that gets frucated. It's just
47:49telling you about hemoglobin that's
47:51glycated. But so if we're going off of
47:53the in vitro studies and we're going to
47:55assume that fructose is let's say eight
47:57times more glycating than glucose. And
47:59this was looking at hemoglobin. So we
48:01already know the interaction between
48:03glucose and hemoglobin creating A1C. And
48:06now if we can assume the fructose and
48:08and hemoglobin and the fation that's
48:10caused there. Since we already know the
48:12difference in reactivity and we know the
48:13amounts of each in the blood at baseline
48:15and even after consuming massive amounts
48:17of fructose, we can very easily infer
48:20how much fruation is going on. And it's
48:22very obvious based on the levels that we
48:24just went through that we would be
48:26getting less fruation from fructose than
48:28we would get glycation from glucose. And
48:30again, we know this based on the study
48:32that we just went through looking at
48:33baseline levels, the first study, and
48:35then the second study looking at how the
48:37increase in fructose after consuming
48:39incredibly high amounts of fructose is
48:42still lower than fasting glucose levels.
48:46And even if we considered the difference
48:48in glycation between the two, the fation
48:50would still be less than we would get
48:52from fasting glucose levels. So with
48:54that in mind, it's obvious that even
48:56though you're not actually able to
48:57measure in a standard blood test the
48:59frucated hemoglobin, it's not actually
49:01relevant and it's going to be less far
49:03far less than the amount of glycation
49:05you would see even from fasting glucose
49:07levels. So with that in mind, it really
49:09nullifies any concerns here when it
49:10comes to fruation. But we're going to
49:12take a look at the study that also uh
49:14corroborates this. This is a study
49:15titled hemogin fruation promotes heen
49:18degradation through the generation of
49:19endogenous reactive oxygen species where
49:22they state in spite of fructose higher
49:24reactivity its contribution to
49:26extracellular glycation has been less
49:28noteworthy than glucose. This is mainly
49:29attributed to the low plasma
49:31concentration of fructose compared with
49:32glucose. So again pointing out exactly
49:35what we're describing here which is that
49:36when we're looking at blood levels it's
49:38really irrelevant and outside of blood
49:40levels everything else is the same uh in
49:43terms of what we described so far when
49:44it comes to glucose you know in terms of
49:46this much broader conversation where you
49:49know when we're comparing glycation and
49:50fruation it's true that fruation isn't
49:53quite as slow as glycation that first
49:55step is about eight times faster but in
49:58general fructose levels in the blood are
50:00so low that that's not relevant when it
50:02comes to the tissues again in a normal
50:03metabolic state, fructose is not staying
50:06as fructose. You're not consuming
50:07fructose and then it just goes into the
50:09uh into all your tissues and just sits
50:11there as fructose and waits for days and
50:13weeks and months to undergo fruation.
50:16We're constantly highly metabolically
50:18active organisms. And so once we get
50:20fructose, a lot of things happen. And
50:22you know, we see this very clearly when
50:24it comes to fructose. And I've described
50:25this in a previous episode talking about
50:28Robert Lustig's fear-mongering regarding
50:30fructose. And so check out that podcast
50:32if you're interested for the details.
50:33But essentially once we get fructose, it
50:35goes to the liver and it's immediately
50:37converted to other products as converted
50:39to glucose. It's converted to lactate.
50:41It's converted to glycogen. It's
50:43utilized uh as fuel and converted to
50:45energy. But it's not just sitting there
50:47as fructose. And so uh it's not really a
50:50concern from that standpoint. Now of
50:53course fructose is a fuel just like
50:55glucose is. And so the inhibition of the
50:58metabolic usage of that fuel will cause
51:02age production because it'll increase
51:03the triosphosphates and that will
51:05increase the dicarbonial production and
51:07that'll increase advanced glycation end
51:08products. But again this is an issue
51:10with the inhibition of the metabolic
51:12function and inhibition of mitochondrial
51:14function not actually the fructose
51:16itself. Again this would happen whether
51:18we're talking about fructose or glucose.
51:20And in this state you also see it
51:21happening with fats and ketones as well.
51:23and you see it happening whether you're
51:24consuming the fuel or not, whether your
51:26body is producing the glucose through
51:27glucogenesis or you're consuming it,
51:31it's going to be a precursor there for
51:33the trials phosphates. So all of that
51:35is, you know, just as relevant to the
51:37fructose conversation. And then along
51:39with that, a general state of impaired
51:40metabolic function and oxidative stress
51:42is going to reduce the detoxification of
51:44glycation products and the clearance of
51:46the advanced glycation end products.
51:48This applies with the fruation products
51:49as well. So again, none of this
51:51implicates fructose as a concerning
51:55glycating agent uh even in the context
51:58of it being eight times uh higher uh
52:01reactivity than glucose when it comes to
52:04the fation capacity with hemoglobin. Now
52:07I do want to touch on one piece here
52:10which is when it comes to looking at
52:11fructose and animal models and this is a
52:16very parallel situation to something
52:17that we've talked about when it comes to
52:19fatty liver when it comes to uric acid
52:21with most of the research looking at the
52:22negative effects of fructose. It occurs
52:24in situations that are entirely
52:26irrelevant to a normal physiological
52:29state situations that are entirely
52:31irrelevant to food and how food is
52:33available because food never uh just has
52:35fructose on its own. It's always paired
52:36with glucose among other things. And
52:39it's also in models and in types of
52:41experiments that are totally irrelevant
52:43to us as humans. And so it is true that
52:46in some studies looking at animal models
52:48with high fructose diets, there is an
52:50increase in advanced glycation end
52:52products. However, like the other
52:55research on fructose that points to
52:56these negative effects, there are some
52:58major flaws here. One is normally there
53:00are large amounts of fructose sweetened
53:02solutions of pure fructose which a is
53:05not absorbed well. So that fructose
53:07feeds endotoxin which then is we'll talk
53:09about later is actually a major driver
53:11of advanced glycation end products and
53:12glycation in general um and oxidative
53:15stress and this whole millu. On top of
53:17that we also just have incredibly high
53:19amounts of fructose. You know, we're
53:21talking sometimes 50% of the diet or
53:23more, which you, you know, in nature,
53:25you never even, even if you're eating
53:26pure table sugar, you can never have
53:28more than 50% of the diet from fructose.
53:31Uh, and so you get these massive amounts
53:33that are basically irrelevant to what
53:36any, you know, normal rodent or human
53:38would eat. Or you have infusion of
53:39fructose where you're getting massive
53:41amounts in the blood that are way higher
53:43than we would ever get from consuming
53:44fructose. And then on top of that, we
53:46have some other issues with these animal
53:48models and rodents in general with these
53:50fructose studies, which is that their
53:52capacity for handling fructose is far
53:55lower. Their liver's capacity for
53:57utilizing and metabolizing fructose is
53:59far lower than us as humans. And so
54:01they're far more likely to have this
54:02buildup of intermediates and increase in
54:05fat production and other negative
54:06effects there. And they also tend to
54:09actually have as a result of this much
54:11higher levels of fructose in the blood
54:13than we do as humans because they don't
54:15utilize it as well. So considering all
54:18these factors, these studies looking at
54:20high fructose diets and rodents
54:22increasing advanced glycation end
54:23products really aren't relevant to us as
54:25humans consuming any sort of normal
54:28food. With all that being said, when it
54:30comes to fructose, there really aren't
54:32any unique concerns when it comes to
54:33fructose and glycation. It's really not
54:36a uh driver here or a culprit here when
54:39it comes to glycation and age
54:41accumulation and aging and chronic
54:43disease states. All right, so we're
54:45going to wrap up part one here. And in
54:47part two, I'll be going over how glucose
54:49and insulin can decrease glycation, why
54:51ketogenic diets can be worse than high
54:53carb diets when it comes to advanced
54:54glycation and product formation. We'll
54:57be going over how autophagy helps to
54:58clear ages, but why increasing autophagy
55:01is not actually the answer. We'll be
55:03talking about the true primary drivers
55:05of age accumulation and the best diet
55:07and supplements for minimizing
55:08glycation. As always, if you enjoyed
55:11today's episode, please leave a like or
55:13comment wherever you're watching or
55:14listening. And also, please leave a
55:16five-star rating. All of those things
55:18really do a lot to help support the
55:19podcast and are very much appreciated.
55:21As always, to check out the show notes
55:23where you can take a look at the
55:24studies, articles, and anything else
55:25that I referenced throughout today's
55:27episode, you can head over to
55:28jfeldmanwwellness.com/mpodcast.
55:31And if after listening through the
55:32podcast, you're not exactly sure where
55:34to get started when it comes to
55:35improving your metabolic health or if
55:37you're just looking for some extra
55:38guidance on any health issues you might
55:40be working on, then head over to
55:41jfeldmanwellness.com/call
55:44where you can sign up for a free call
55:45with a member of the Jfeldman Wellness
55:47team who can provide you with insights
55:49and next steps for you to take on your
55:51health journey. So again, head over to
55:52jfeldmanwwellness.com/call
55:55to sign up for a free call. And with
55:57that, I'll see you on the next one.

About this transcript

This page contains the full transcript of What REALLY Causes Glycation (Is Sugar Really the Problem?) (EB # 137) by Jay Feldman Wellness, generated from the public captions YouTube serves with the video. The transcript has 10,760 words across 1,644 segments, with the original timestamps preserved so you can click any line to jump to that moment in the embedded player.

What you can do with it

Use the transcript to take notes, quote the speaker, build a study guide, generate a summary with ChatGPT or Claude via the YouTube Summary tool, or export it as a timed subtitle file with YouTube to SRT. You can also re-open it in the transcriber to choose a caption track available on the video.

Free YouTube transcript tool

YouTube2Text is a free YouTube transcript generator — no signup, no daily limit. Paste any YouTube link and get the full transcript instantly, with timestamps, click-to-jump, caption language selection, AI prompts for ChatGPT, Claude, and Gemini, and exports to TXT, SRT, VTT, or Markdown.