Artificial Sweetener, Erythritol

Erythritol and Heart Disease

Who uses the artificial sweetener, erythritol?

Here is a minimally altered report by F. Perry Wilson, MD, MSCE, Feb. 28, 2023.

This is not my usual blog, in which my comments are my own words:
The first section (A) is my paraphrase of Dr. Wilson’s opening segment.
The 2nd section (B) is an extensive, direct quote from the body of Dr. Wilson’s report.
The 3rd section (C) is my “take” on overeating, obesity and the disease cascade which results from overconsumption of foodstuffs.

The reasons why I am doing it this way are that:
– The “body” of Dr. Wilson’s report is already succinct: my paraphrasing of the entire paper would detract from his message, while gaining little in terms of brevity.
– His diagrams and their explanation however, are instructive and important.
– Our society’s approach to the problem of foodstuff overconsumption is counterproductive: in “THE BOTTOM LINE” (C), I propose a solution.

(A)

ARTIFICIAL SWEETENER, ERYTHRITOL

The artificial sweetener, ERYTHRITOL, a sugar substitute derived from corn, is also found in many fruits, including peaches, pears and watermelons: our bodies make some too. It is used in many food products, including chocolate, chewing gum, beverages, baked goods and other items.
A recent article warns us of the dangers of erythritol, noting a survey in the USA, which showed the following consumption of erythritol among the population surveyed (Fig 1).

Population group	Grams /day, mean	Grams / day, 90th %	Grams /day, 95th %
Children, 1-12 years	5.9	13.2	15.8
Boys, 13-19 y.o.	7.6	19.3	15.8
Girls, 13-19 y.o.	7.3	15.6	15.8
Males, 19-65 y.o.	5.5	12.8	18.9

“Sugar Substitute Linked to Heart Disease”, is by F. Perry Wilson, MD, MSCE, 2/20/23.
I have paraphrased it and removed two statistical diagrams, to make this note shorter and more understandable, for my lay readers.

(B)

Dr. Wilson begins
He reminds us of our modern predilection for high-calorie, high salt, high sweetness foods, in which sucrose (cane sugar) is replaced with sugar substitutes: a line of small molecules and polypeptide artificial sweeteners and so-called “natural” sugar alternatives, which together constitute a $10 billion–dollar industry,

He says: “Is This Thing You Eat Everyday Secretly Killing You?”, targeting Erythritol, a sugar alcohol equalling sucrose in sweetness, which is found in corn and is therefore “natural”, allowing manufacturers to claim “no artificial sweeteners”.

Erythritol is rapidly absorbed from the small intestine and excreted mainly in the urine.
It is not metabolized either by our tissues or by bacteria, so it doesn’t contribute to tooth decay, doesn’t raise blood sugar, doesn’t supply energy and doesn’t cause obesity. Overall, it sounds like an ideal substitute for sugar.
However there is a hidden problem: according to an article in Nature Medicine,
Erythritol may contribute to heart attacks.

Dr. Wilson goes on to say (here, I quote directly from his report, including his relevant diagrams, with only minimal adjustment of syntax and punctuation):

“The researchers started with a metabolomic analysis of just over 1,000 people being assessed for heart disease.
Modern metabolomic studies look at the levels of hundreds, sometimes thousands, of metabolites circulating in the blood to see which might be associated with a given disease.
In this case, focusing on sugar and sugar-substitute metabolites, erythritol topped the pack.
Those who were observed to develop a major adverse cardiovascular event, had significantly higher erythritol levels at baseline than those who did not.

There are two problems with this: First, because metabolomic studies check so many metabolites, a few “strong hits” are guaranteed just by chance alone.
Therefore results of investigations need to be validated by replicating the tests.
The authors did this, showing in an independent American dataset that those in the highest quartile of erythritol levels were much more likely to have a major heart event eventually.

Figure 2: red line shows the 3-Year survival of people with the highest erythritol blood level.

Of course, just because erythritol levels are higher in people who go on to have heart attacks doesn’t mean that erythritol causes the heart attacks.
People who consume sugar substitutes may be different in important ways compared with those who don’t; think about factors like diabetes, obesity and even socioeconomic status.
The authors adjusted for many of these, but as we’ve said many times before, perfect adjustment is impossible.

The authors clearly wanted to ask – If erythritol has a causal link to cardiovascular disease, what‘s the mechanism?
They hypothesized that erythritol in the blood might stimulate platelets to clump together and clot, more easily.
Sure enough, that’s just what they found.
In a test tube, as the concentration of erythritol increased toward 45 micromolar, platelets began to get stickier.”

In an experimental model of time-to-carotid artery occlusion, mice given erythritol had faster clotting in arteries (Fig 3, copied from Dr. Wilson’s report).

Figure 3: “Vehicle” is the liquid in which the artificial sweetener, erythritol, was dissolved.
Mouse carotid arteries were completely blocked by clot less than 10 minutes after the solution was injected

Dr. Wilson continues:
“Okay. If there’s one thing I’ve learned from reading studies of artificial sweeteners, it’s to check the concentrations. It’s one thing to say that a given sweetener causes cancer in rats who are fed 100 times the typical daily dose. It’s quite another to say that this occurs when the dose is at physiologic levels.
So, 45 micromolar — that’s the concentration where all this platelet action is seen – can we put that in context?
Well, in the American validation cohort, the highest quartile of erythritol levels comprised people with levels ranging from 6 to 46 micromolar. So, right off the bat, it’s clear that 45 micromolar is on the high side. 
Of course, maybe you don’t need erythritol levels to be 45 micromolar all the time; maybe just spiking for a while can increase clotting. To assess this, the researchers measured erythritol blood levels in eight healthy controls after consuming 30 g erythritol (Fig 4).”

Figure 4, from Dr. Wilson’s report: Bood levels of erythritol get incredibly high and stay above 45 from about 30 minutes to 2 days after ingestion of Erythritol, 30 g.
30 g of erythritol raises the blood erythritol level to >45 µmol, in all 8 people, within half an hour.
The erythritol level does not go below 45 µmol until one day after ingestion and does not return towards minimum levels for between 3 and 7 days.(Wikipedia says that 80% is excreted in the urine within 24 hours, but that does not disprove Dr. Wilson’s report).
So if the above diagram is right, at 30 g daily, your blood level would go like this (+/-):

DOSE	30	30	30	30	30	30	30
Level	50	75	87.5	93.8	96.9	98.4	99.5

Dr. Wilson continues:
“If we want to put this together, we can probably say that you might not want to eat or drink 30 g of erythritol every day. The authors argue that 30 g is exactly what we’re taking in per day, citing an FDA filing, but I checked that: 30 g is actually the 90th percentile of intake in the United States, with the mean reported at 13 g.

Even 13 g seems too high. This food diary study from Europe estimates daily intake at about 5 or 6 g. And that’s among people who reported using all sugar-free products in their daily consumption.”

Figure 5: consumption of erythritol in Europe (from Dr. Wilson’s report).

Dr. Wilson continues:
“So, no, I’m not terribly worried right now about my monkfruit sweetener, my sugar-free gum or my toothpaste.
While the harms from sugar substitutes are still mostly theoretical, the harms of sugar are all too real.
Erythritol may well be the lesser of two evils here.
It would be great to have all the sweetness of sugar and none of the harms.
Of course, I’m reminded of a truism when it comes to the science of diet: It’s rare that you can have your sugar-free cake and eat it too.”

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson, and his new book, How Medicine Works and When It Doesn’t, is available now.

(C)

THE BOTTOM LINE (Dr. Harry)

The message from this article is clear: too many of us attempt to sidestep the triple threat of obesity, hypertension and diabetes, while avoiding the self-control necessary to stop overeating.
Clearly the conclusion that sugar is the cause of obesity, while perhaps correct, has led us to avoid sugar while indulging our desire for more food than we need.
It’s tempting to offer platitudinous advice, such as “Too much of a good thing is good for nothing”, “Don’t jump over a precipice to avoid a tiger”, “Practice moderation in all things” or “Maintenance is cheaper than repair” ………… I could go on, but there is a practical way.

Don’t ask “How can we fix this?” – ask, “Why is it this way?”

We can do better than to concentrate on “How can we fix this?”.
Instead, we should figure out “Why do so many of us have such an urge to eat?” and
“Is there some way of reducing the urge?”, because the question leads to the answer.

The answer is in our metabolism: the “raison d’être” of our increased appetite, reduced basal metabolic rate and lassitude is our uncompensated high-stress modern life, which leads to hypercortisolemia, resulting in intracellular hypothyroidism
(intracellular “T3 starvation”), with lassitude, reduced BMR and weight gain.

THE HORMONES:

Ghrelin, often called “the hunger hormone”, stimulates the appetite. It is released by the empty stomach and is said to be lower in obesity.
It also reduces thermogenesis by our brown-fat cells, thereby reducing energy consumption and encouraging storage-fat growth.
Ghrelin secretion increases in parallel with cortisol following psychological stress (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682420/).

Cortisol: stress triggers increased cortisol production and cortisol triggers
– blockade of Triiodothyronine (T3) production,
– destruction of existing T3,
– higher Ghrelin production, with increased appetite, reduced fat-burning and reduced basal metabolic rate,
– lassitude, with reduced energy expenditure and weight gain.
The result is the “couch potato” syndrome.

STRESS REDUCTION

Stress reduction, in our now-worldwide civilization, is extremely difficult (if not impossible) to achieve, so we have no way of directly reducing cortisol production.
We can however supply our cells with Triiodothyronine (T3), which will return our metabolic rate to normal and cancel the psycho-cognitive effects of “T3 starvation”.
In this way the perceived stress can be lowered, resulting (hopefully) in a reduction of Cortisol, reduction of Ghrelin, reduced appetite and weight loss.

The recurring theme: “intracellular T3 starvation”.

We are thus back to an argument which I have made before: evaluation of “thyroid profile” should be routine in the assessment of all symptoms and syndromes, so that “T3 starvation” (intracellular hypothyroidism) can be diagnosed and treated.
Doing so would eliminate a major factor in the development of our diseases, including overeating, obesity, hypertension, psycho-cognitive deterioration and reduced myocardial efficiency.

So, rather than trying to avoid obesity by assuaging our hunger/overeating-disease problem with nonfattening, poisonous sweetners, which don’t prevent obesity anyway, why not investigate the reasons for hunger, correct our hormonal aberrations and enjoy our sugar-sweetened snacks?

So we don’t need to avoid sugar

Instead, let’s change our ways and do as follows:

• Assess cortisol production, BMI, BMR, T3 and rT3 metabolism.
• Normalize thyroid hormone metabolism by treating with triiodothyronine, thus reducing Ghrelin secretion, improving the basal metabolic rate and resolving the lassitude problem: this will slowly improve the BMI.
• Stop using artificial sweeteners: if you want sweet foods, sweeten with sucrose.
• Assess hormone balance and correct such problems as may be discovered.
• Particularly, correct DHEA deficiency and increase exercise level, so as to convert fat stores to muscle tissue and correct progesterone deficiency, so as to improve sleep and reduce the tendency to anxiety and depression.
  

REFERENCES

Sweetener Review: Erythritol | Is it Really “Natural” and The Perfect Sweetener?
https://www.whatsugar.com/post/is-erythritol-natural-or-artificial

Yet Another Worry — This Time It Is Erythritol McGill University. Office for Science and Society: Separating Sense from Nonsense
https://www.mcgill.ca/oss/article/health-and-nutrition/yet-another-worry-time-it-erytritol

Erythritol: Is This ‘Healthy’ Sweetener the Real Deal? By Dr. Josh Axe, DC, DNM, CN
March 1, 2023 https://draxe.com/nutrition/erythritol/