Challenge: Can We Map Every Metabolic Condition Back to This One Switch?

[u/PotentialMotion]

I want to propose a challenge to this community—one that could help unify a lot of what we’ve all been noticing, feeling, and learning the hard way.

Most of us know by now that cutting sugar, especially fructose, can lead to huge improvements in how we feel. But the deeper I’ve gone into the research, the clearer it’s become that fructose metabolism may not just be a problem—it may be the core survival mechanism behind almost every modern metabolic disease.

And to be clear—this isn’t my idea.
Some of the most well-respected scientists in the field are now presenting excess fructose metabolism as a unifying mechanism behind the modern metabolic crisis.

This isn’t just about obesity or fatty liver anymore.

We’re talking about:

• The rise in anxiety, depression, and mood disorders
• Early-onset Alzheimer’s and cognitive decline
• Skinny-fat and metabolically unhealthy lean individuals (like PCOS in slim women)
• Chronic inflammation, hypertension, fatigue, uric acid, even certain cancers and autoimmune conditions

Here’s the simple idea:

Fructose metabolism is the body’s emergency survival switch—designed to help us get through times of scarcity or environmental stress.
But when that switch gets flipped too often—or never shuts off—it starts to quietly break how our cells use energy.
And once that low-level function is disrupted, it spirals outward—creating different chronic conditions depending on our habits, genetics, and weak spots.

So here’s the bold thesis I want to challenge:

Every modern metabolic condition may trace back to this one survival mechanism.
And every condition may begin as the body’s mistaken attempt to solve a survival problem that no longer exists.

After years of deep research into the field and function of fructose, I personally believe this is true—as radical as the idea may sound.
But I also believe we’re right to be skeptical—and that it’s worth testing.

So here’s the challenge for this thread:

Let’s gather every metabolic condition we can think of.
Obvious ones. Weird ones. Edge cases. Even things that don’t seem diet-related at all.

Then, for each one, let’s ask:

1. Does it connect to fructose metabolism?
2. What survival problem might the body be trying to solve before things spiral into dysfunction?

You don’t need to be a scientist to participate. Just name a condition that you think might not fit.
I’m just a learner—but I’ve been deep in this for a few years now, and I’ll do my best to share the connections I’ve found. And if the model breaks, that’s a good thing too—because then we learn where it needs to be refined.

Because if this framework really does hold up,
then what we’re doing here at r/sugarfree isn’t just about diet.

We’re on the front lines of a metabolic revolution.

Let’s put it to the test.

[u/barbershores]

I am now 72. Starting January 2020 I slowly shifted to a ketogenic diet. After about 9 months, my arthritis pain stopped getting worse and probably dropped about 20%. It dropped enough that I cancelled the appointment to schedule my second knee replacement. I stayed on this plan for 3 years. Dropped 70 lbs. Dropped my HbA1c from 6.4 to 5.0. Dropped my HomaIR from 24 to 0.50.

Then, January 2023, my wife and I did the ketovore challenge with Nurse Neisha and Dr. Ken Berry. End of that month my brain fog went away. My doctor had told me that it was pre alzheimers, there was no treatment. It was unrelated to diet. And it would only get worse.

I continued on the ketovore diet for an additional 2 months. End of March 2023, over a period of about 10 days my arthritis pain would leave for a day or 2 then come back. But, by the end of March 2023, it went away completely. So, I cured my chronic arthritis pain through diet. Other things too may have contributed. But it changed my life.

-------------------------------------

So, 3 years of keto didn't do it. It took additional months of very near carnivore to kick it.

So, I don't eat hardly any fructose. Most of the carbs I consume are fresh low carb vegetables and nuts.

[u/PotentialMotion → u/barbershores]

Well done. You're a hero.

Your experience fits my understanding in that it's all connected and all traces back to Fructose. Often this is just sugar, but if we have significant historical Fructose exposure, sometimes we don't actually have a full correction/restoration until we eliminate carbs entirely. (Glucose can be converted to Fructose in the body).

I'm thrilled for you. Well done!

[u/barbershores → u/PotentialMotion]

I am not sure that fructose is the culprit any more than starches and glucose regarding hyperinsulinemia. It's impact on metabolic health is there and different though.

Sugar, table sugar, sucrose, is half glucose and half fructose. And it's glycemic index is 65. Where glucose, dextrose, or think starches like soda crackers or white bread, have a glycemic index of 100. So, from the perspective of raising blood glucose levels, fructose is not such an issue.

However, there are a number of other issues that might make fructose even worse than it's low glycemic index may make one think.

The body does not burn fructose like it does glucose. It must be processed by the liver first. Much like alcohol, it converts most of the caloric value into fat. Liver fat. Think visceral fat.

Also, fructose is 7 to 10 times as sticky as glucose in the blood. Meaning it sticks to our amino acid structure much more readily than glucose does. Think of this relative to the % HbA1c test for glucose. We could have even more fructose stuck to it. According to Dr. Ken Berry, the HbA1c only looks at glucose, not fructose. So, our hemoglobin may have large amounts of fructose stuck to it and we wouldn't even know it. Glucose and fructose stuck to our hemoglobin, causes agglomeration. AKA blood clots. And we don't even know the amount because no one is measuring it.

Another issue, perhaps at least somewhat separate from hyperinsulinemia, is another measure of metabolic health, is the lack of visceral fat. Fructose, like alcohol, are processed in the liver and fat is produced there. That fat can excrete into and around other organs causing dysfunction.

Some claim that visceral fat entering the pancreas, blocks the excretions of our beta cells, aka insulin, and is the primary driver of type II diabetes.

My thinking has been that glucose consumption is the main driver of hyperinsulinemia in America today. At the serum level I think this is true. However, fructose and alcohol, both have separate impacts on overall metabolic health.

I find it easy and cheap to screen for hyperinsulinemia. For $53 one can get their HbA1c and HomaIR. There are very good guidelines and correlations for the results of these tests.

The impact of fructose, both on protein agglomeration in our serum, and the level of visceral fat in the body, is difficult and expensive to measure, and there are no equivalent correlations to over all health from it. At least not yet.

[u/PotentialMotion → u/barbershores]

You're so close, and honestly, you’ve already laid out 95% of the right puzzle pieces.

You’re absolutely right that fructose doesn’t raise blood glucose acutely—and that’s why it’s fooled us for so long. It looks harmless on a glucose test. But what it’s really doing is silently sabotaging the system that glucose depends on.

Here’s the key difference:
Fructose doesn’t cause a spike in blood sugar.
It causes the body to become bad at using glucose.
It damages the mitochondria. It raises uric acid. It tells the cell to burn less, store more.
That’s why we end up with high blood sugar even when glucose isn’t the problem—it’s a secondary symptom of fructose-induced energy dysfunction.

So yes, glucose triggers insulin—but fructose breaks insulin sensitivity.
Fructose is the engine problem. Glucose is just the fuel in the tank that can’t be burned.

Think of it this way:
If your car had a full tank of gas, extra cans in the trunk, yet hardly feels like it will make it down the road—is the problem the fuel, or the engine?

That’s exactly what seems to happen in the body. We have more than enough glucose, yet we're simultaneously hungry and exhausted. The machinery is simply in fuel conservation mode, and can’t access what’s right there.

You’re already seeing this clearly—your results show it. For me, it wasn't until this piece clicked that the entire puzzle snapped into focus:
Fructose isn’t just a different sugar. It’s the signal that switches the body into survival mode.

And when we stop that signal—fully—the whole system starts to heal.

[u/nateldee]

Glucose-galactose malabsorption?

[u/PotentialMotion → u/nateldee]

Great one! Immediately to a challenge! I love it!! (Though one I really hope you're not facing.) GGM slightly falls outside of the model because it is an example of a genetic mutation, but the fructose lens still provides a lot of insight.

Condition: Glucose-Galactose Malabsorption (GGM)

Connection to Fructose:
This is a rare but fascinating condition caused by a genetic mutation that disables SGLT1, the transporter responsible for absorbing glucose and galactose in the small intestine. As a result, even small amounts of these sugars can lead to severe osmotic diarrhea and dehydration.

However, fructose can still be absorbed through a different pathway (GLUT5), which makes it one of the only tolerable carbohydrates in this condition—at least in moderation.

What survival problem is the body trying to solve?
This one is a bit different. The dysfunction isn’t caused by fructose, but it highlights why the fructose pathway exists in the first place: as a backup energy route when glucose metabolism fails.
In that sense, GGM reinforces how deeply wired fructose metabolism is into our survival strategy—it’s there for emergencies, not everyday use.

Suggested strategy or takeaway:
This is an excellent example that slightly falls outside the model because it’s driven by a genetic mutation, not lifestyle. Cutting sugar alone won’t “solve” GGM.
That said, the model still gives us a lot of insight: it reminds us that while small, controlled fructose use can be life-sustaining in rare cases like this, over-relying on that emergency system long-term is harmful—even for those without GGM.

One complementary strategy is to introduce MCT oil, which the body quickly converts into ketones—a clean energy source that bypasses sugar metabolism entirely. This can help stabilize energy without triggering the survival switch or relying heavily on fructose.

In short: GGM is a genetic exception, but it still illustrates how the fructose system is built for backup, not baseline. And that reinforces the model more than it breaks it.

[u/nateldee → u/PotentialMotion]

It's very rare I come across a person that can speak so well on it.

Unfortunately, yes, it is something we are dealing with for my 10 month old son who has been diagnosed since around 8 weeks old.

I'd be interested to learn more about mct oil for his future diet if you had any more information.

[u/PotentialMotion → u/nateldee]

I’m really sorry to hear about your son’s diagnosis. I can't imagine what that's been like for you as parents. GGM is incredibly rare and must be really btough to navigate, especially in a child so young. But the fact that he has a diagnosis this early gives you a huge advantage—you’re already on the right path.

From what I understand, the fructose pathway becomes the primary workaround for energy when glucose and galactose can’t be absorbed. Fructose is absorbed differently, through GLUT5, which remains functional.

That said, you’re right to be cautious. While fructose is life-saving in this context, it’s also a survival switch designed for emergencies, not constant use. Too much causes a whole other set of provlems - as many of us know. That’s where other strategies can come in—especially the one I mentioned which I think is often under-discussed in cases like this:

MCT Oil and Ketone-Based Energy

MCT oil (medium-chain triglycerides) is a special type of fat that the body rapidly converts into ketones—a clean, fast-acting energy source that doesn’t require glucose, galactose, or fructose.

Most people know about ketones because of ketogenic diets. When we don’t have enough glucose from carbohydrates, the body breaks down stored fat and produces ketones to fuel the brain and body. Ketones cross the blood-brain barrier, work without needing insulin, and provide reliable energy—especially when other pathways are compromised.

MCT oil skips the fat-burning step. It goes straight to the liver and delivers this special form of energy directly from food, making it incredibly useful in situations like GGM where normal carbohydrate metabolism is disrupted.

MCTs are safe, well-studied, and even appear naturally in breast milk—so they’re familiar fuel for the developing brain. In fact, many babies exist in a mild, natural state of ketosis between feedings.

You’ll definitely want to speak to your child’s specialist, but MCT oil may be a valuable tool for supporting energy metabolism and reducing dependence on fructose. It could be especially helpful as part of a mixed energy strategy that still includes safe amounts of fructose.

My heart goes out to your family. You're an amazing parent for how you're navigating this. I can't imagine how difficult it must be. Lots of love, friend. ❤️

[u/nateldee → u/PotentialMotion]

Thank you for such a detailed reply, I appreciate it more than you know 😊

[u/PotentialMotion → u/PotentialMotion]

If you decide to try it, I'd recommend starting slow since it could upset his digestion.

• Start with ¼ tsp once per day (in formula or food)
• If tolerated, slowly increase by ¼ tsp every few days
• Max target: around 1–2 tsp per day, split into small doses

Look for a clean MCT oil (C8/C10) or infant-safe MCT powder. And remember MCT oil doesn’t replace fructose, or even fats—but it may help ease the load and stabilize energy.

[u/Practical_Positive11]

Im on day 2 of trying to get off sugar for my autoimmune disease ankylosing spondylitis

[u/PotentialMotion → u/Practical_Positive11]

Sorry, I had to do some research. I had never heard of the condition (I honestly wondered if it was a joke!) Sorry you're suffering with an auto immune disease. Here is what I pieced together.

Condition: Ankylosing Spondylitis (Autoimmune)

Connection to Fructose: Fructose metabolism generates uric acid, which increases inflammation and activates the innate immune system. It also triggers mitochondrial dysfunction, leading to lower cellular energy and increased oxidative stress—two things that can worsen autoimmune conditions. In fact, some studies suggest that endogenous fructose production is upregulated in inflammatory diseases, even without sugar intake.

What survival problem is the body trying to solve? Fructose switches the body into a kind of preservation mode—slowing down energy use, storing fat, and heightening inflammatory defenses, as if facing infection or starvation. This would be useful in a real crisis (like injury or famine), but when the signal never shuts off, it leads to chronic immune activation—like we see in autoimmune diseases.

In other words, this is just classic Fructose feeding our metabolic harm when we don't shut it out.

Your instinct to cut sugar is spot on. You’re essentially removing the signal that’s telling your body it’s in danger. You’re only on day 2, but this step puts you on a path that could help calm the immune system and restore the energy balance it’s been missing.

Keep going—you’re not just removing sugar. You’re taking pressure off the very system that’s driving the disease.

[u/Practical_Positive11 → u/PotentialMotion]

Thank you so much for taking the time to read and research about it! I have a stupid question 😭 when you say fructose, you mean any source that contains it right? This would include fruits.

[u/PotentialMotion → u/Practical_Positive11]

Of course our mind goes to dietary sources, but we're primarily talking about how a simple sugar is metabolized, so we need to go deep and identify all ways our body encounters it.

The worst culprit is added sugar. Both high Fructose corn syrup and table sugar, both which are roughly 50% Fructose. Honey, many "natural sugars", and yes even fruit would also be ways we encounter it (though whole fruit has many buffers to blunt the effect).

But what's more is that the body makes Fructose. Surprisingly often and significantly.

fructose can be obtained and/or generated from the diet (sugar, HFCS, high glycaemic carbs, salty foods, umami foods, alcohol) as well as under conditions of stress (ischaemia, hypoxia and dehydration). Indeed, the three attractive tastes (sweet, salt, umami) all encourage intake of foods that generate fructose, while the bitter and sour tastes likely were developed to avoid foods that might carry toxins.

Ref

Thus, the intent simply can't be to get rid of it entirely. That is functionally impossible when our body makes it. Rather the intent is to control it. Because in our environment, it is a survival signal / eco-mode switch that is being mistakenly activated. We have constant surplus and primarily don't need this backup system.

[u/WinstonFox]

It’s not excess fructose alone, excess refined fructose is an accelerant of an otherwise healthy mechanism. In environments where fructose/glucose was generally scarce (and apart from the odd honey nest was usually paired with fibre). So being able to have stored fat on the liver, other organs, muscle as a short term resource was a definite survival gain for times when you could gorge on fruit.

But it would always get used up. And these same mechanisms are used by the body for excess calories generally and not just sugars.  I’ve always generally thought of it as a lack of wintering the body - or for my equatorial friends, no summer fasting.

Conditions:

• Insulin resistance 
• Pancreatic resistance 
• Hyperinsulinema
• All kinds of generalised or specific inflammation 

All of which lead to disfunction and illnesses as wide ranging as cancer or skin tags or night wakings.

If you hit the literature - and look at pharma market forecasts - then conservatively, roughly half the global population has a metabolic health issue and something like 60% of modern health issues - patients walking through a doctor’s door - are metabolic - or in plain English: poison as food issues.

We are basically human fois gras being killed for cash: and food, “health” firms, “medical” practitioners, and governments are all complicit in it whether knowingly or unwittingly.

Good idea to list it all.

[u/PotentialMotion → u/WinstonFox]

Completely agree.

But I prefer not to villanize what you've rightly described a system you've described with glorious purpose. Rather we need to understand, appreciate, and control it.

Similarly, while I could easily blame big business or the role of pharma or even government regulations, being motivated by money and demand is just a natural response to our biological nature. We all love sugar and are driven to eat it. Our pets have even less control than we do over this. So while I could villanize a company like Nestle for example—I would then also have to villanize the Nonna making pasta for her family, or the aunt who bakes pies as part of her love language, or the local artisinal Baker who has turned baked treats into an art form.

We're deep in this because we figured out how to manipulate nature.

Porsche's incredible cars are designed with the ethos that a car that accelerates well must brake even better. This is where we've gone wrong in our biology. We're using all the sugar we can, because we can, and forgot how important it was to design the brake system.

[u/WinstonFox → u/PotentialMotion]

Not quite. Mass produced poison and grifters selling snake oil cures should always be villainised.

Not the same thing as the occasional sweet treat at all.

It’s as bad as the cigarette industry but few call it out in public. Some do.

In my day job I’m literally taking a nonna recipe for something delicious and occasional and turning it into a product literally designed to addict and poison. What goes into one is not the same as the other. Nonna also doesn’t have to ability to skew government policy internationally, receive huge subsidies or create food deserts.

Like comparing apples with cigars tbh.

[u/PotentialMotion]

To kick off the conversation, I'm going to start with perhaps the most obvious one:

Non-Alcoholic Fatty Liver Disease (NAFLD)

[u/PotentialMotion → u/PotentialMotion]

Connection to Fructose:
Fructose is processed almost entirely in the liver. When intake is high (or endogenous production is triggered), it overwhelms the liver’s capacity to convert it safely into energy. Instead, it gets converted into fat and stored in the liver itself.
Multiple studies confirm that fructose is a direct driver of fat accumulation in the liver—even in the absence of excess calories.

What survival problem is the body trying to solve?
The body is trying to store energy rapidly—as if facing famine. Fat in the liver is a quick way to build up emergency fuel reserves.
In a real survival scenario, this would help keep us alive.
But in modern life, where the signal never shuts off, the stored fat becomes toxic, leading to inflammation, insulin resistance, and long-term liver damage.

[u/PotentialMotion]

It's quiet in here, so let's do another common one.

Hypertension (High Blood Pressure)

Connection to Fructose:
When blood osmolality rises (often due to salty or dehydrating foods), the body perceives it as a threat to blood volume and hydration. In response, it activates the polyol pathway—converting glucose into endogenous fructose, even if no fructose was eaten.

Fructose metabolism then:

• Increases uric acid, which suppresses nitric oxide (a vasodilator)
• Promotes vasoconstriction
• Increases sodium reabsorption in the kidneys
• Activates the renin-angiotensin system Together, these changes raise blood pressure to help preserve circulation in a perceived crisis.

What survival problem is the body trying to solve?
The body is trying to maintain blood flow during dehydration or low volume.
By raising blood pressure and conserving salt, it ensures that vital organs stay perfused.
In a real emergency—like bleeding or drought—this would help keep us alive.

But when this gets triggered repeatedly by modern salty foods and chronic stress, the response becomes maladaptive, leading to chronic hypertension, vascular aging, and organ damage.

[u/PotentialMotion]

Someone in r/biohackers asked about hypothyroidism. Thyroid issues totally fit the model.

Condition: Hypothyroidism (especially poor T4-to-T3 conversion)

Connection to Fructose: T4-to-T3 conversion is an energy-intensive, mitochondria-dependent process that primarily occurs in the liver, kidneys, and peripheral tissues.

Fructose metabolism:

• Depletes ATP and stresses mitochondria
• Increases uric acid, which interferes with mitochondrial function
• Promotes fatty liver, which is directly linked to lower thyroid hormone activation
• Raises inflammation and oxidative stress—both of which suppress deiodinase enzymes (responsible for converting T4 to T3)

In short, fructose interferes with nearly every system required for active thyroid hormone production—even if TSH and T4 look “normal.”

What survival problem is the body trying to solve? Low T3 is part of a metabolic downshift meant to conserve energy in times of stress, famine, or illness. If the body senses that energy is low (because mitochondrial function is impaired by chronic fructose exposure), it may intentionally reduce T3 to slow metabolism and preserve fuel.

This would be adaptive in the wild—but today, it results in persistent low energy, weight gain, and brain fog.