Rethinking Sugar's Harm - how processed sugars drive gut dysbiosis and metabolic disfunction, while natural sugars protect health

Sugar is bad for you, but not for the reason you think. Sugar is NOT bad for you because it raises your blood sugar. Sugar is bad for you because it causes dysbiosis in your gut => increases endotoxin =>inflammation/metabolic dysfunction.

From the outset, it's important to point out that "naked sugar" (think table sugar= sucrose and high fructose corn syrup) has different effects in the body than sugar consumed as a part of fruits/fruit juice/honey etc.. we'll get to this eventually...

Most believe that "naked sugar" is bad for you because if raises your blood glucose, but there is a dearth of evidence to actually suggest that raising your blood sugar is harmful for humans at all independent of pre-existing diabetes (PMID: 30249012).

Though glycemic variability may indicate underlying metabolic dysfunction, it's the metabolic dysfunction that's the issue, not the increase in blood glucose per se.This is a very important point.

The idea that metabolic dysfunction (aka insulin resistance) arises from raising your blood sugar is also not supported by medical research.Insulin induced insulin resistance simply does not happen to any meaningful extent in humans (outside of insulin producing tumors like an insulinoma, or administration of IV insulin), and it certainly is NOT the cause of our current diabetes epidemic.

There are many examples of free living humans that make the majority of their calories carbohydrates - no free living population of humans (=not eating ultra-processed foods) shows evidence of insulin resistance. For instance, consider the Hadza of Tanzania for whom honey is the most desired food, and which accounts for 10-20% of their diet in the rainy season (in addition to sugar from fruit, which they relish) - exceptional metabolic health and I have spent time with them. (PMID 19350623, 27723159). Or consider the Tukisenta of New Guinea, who eat a diet of 90% carbohydrates and remain lean, fit, and metabolically healthy (PMID: 4718949). And the Mbuti hunter gatherers of the Congo who also treasure honey and eat it as the MAJORITY of their calories in the rainy season but remain metabolically healthy year round. (PMID: 24746602, 5009122)

Thus, there are many examples of humans eating "sugar" and/or raising their blood sugar frequently that do not result in metabolic dysfunction/insulin resistance.Though blood sugar is elevated in diabetes, this is a SYMPTOM and not a cause. Full stop.

Now that we have that out the way, let's get to why "naked sugar" (sucrose, HFCS) is harmful. There is ample evidence that "naked sugar," aka processed sugar leads to increased endotoxin- also known as LPS (a component of the gram negative bacterial cell wall)- in the body.

Sucrose or HFCS consumption leading to increased endotoxin levels (known as metabolic endotoxemia) has been shown in both humans (PMID 37764821, 36119103) and animal models (PMID: 25502558, 32804018).

There is also clear evidence that higher levels of endotoxin in human serum correlate with insulin resistance/metabolic dysfunction, inflammation, and obesity (PMID: 21636801) Administering endotoxin to humans intravenously also leads to insulin resistance and inflammation of adipose tissue (PMID: 19794059)

Conversely, giving humans or animals sucrose containing foods like honey, fruit, or fruit juice does not increase levels of endotoxin, lead to insulin resistance, or inflammation.

In one study, two different types of honey were shown to REVERSE inflammation caused by sucrose and HFCS in rats by affecting the gut microbiome, thus decreasing levels of endotoxin (PMID: 34980392). Very cool, right? This is likely because honey contains MANY compounds which prevent the dysbiosis induced by "naked sugars."

While we are talking about honey, I must also point to a study in humans showing that administration of honey IMPROVED metrics of glucose tolerance over an 8 week period (PMID:19817641). This stands in stark contrast to sugar/HFCS which are known to worsen these metrics in humans.

Similarly, both orange juice (PMID: 20200256) and "cloudy" apple juice (PMID: 38906893) have been shown to attenuate increased endotoxin levels caused by "naked sugars."

"Healthy" eating patterns which include fruit and berries have also been shown to be associated with lower endotoxin levels in humans (PMID: 28747701).

So there's pretty clear evidence that "naked sugars" like sucrose and HFCS cause dysbiosis, leading to increased levels of endotoxin -> inflammation, insulin resistance, etc. AND there's pretty clear evidence that foods containing sugar like honey, fruit, fruit juice actually do the opposite- mostly likely because of the hundreds of compounds they contain which PREVENT overgrowth of harmful bacteria in the gut, mitigating increases in endotoxin.

There's also historical data of free living humans (hunter-gatherer types) who eat LOTS of honey/fruit or carbohydrates in general (certainly "spiking" their blood sugar) and do NOT develop evidence of insulin resistance, obesity, etc..

It's ALMOST as if eating foods that occur in nature is good for us (how simple and elegant?), while eating foods that have been overly modified/processed leads to disease. BUT if I say that I will surely be derided as believing some sort of hocus-pocus naturalistic fallacy.

With this thread I am NOT saying that diabetics should not be intentional about consuming honey or fruit/fruit juice. I AM saying that honey, fruit/fruit juice did NOT make someone diabetic, but "naked sugars" like sucrose and HFCS certainly could.

This is a VERY important distinction and I think the mechanisms underlying why "naked sugars" cause insulin resistance and honey/fruit do not are fascinating. If you have diabetes you MUST get rid of "naked sugar." If you have diabetes, it's also reasonable not to over consume honey/fruit but some moderate amount of these could actually be helpful at the level of your gut microbiome. If you take nothing else away from this, I hope this thread will serve as a discussion starting point pushing back against the notion that anything that raises your blood sugar is harmful for you. That position is oversimplified and not supported by the literature. Now go eat an orange or try a teaspoon of honey from a local farm. You're welcome.

Source: https://x.com/paulsaladinomd/status/1898850810055790612 (Paul Saladino)