December 14, 2020

Nutritional Biochemistry

#141 – AMA #18: Deep dive: sugar and sugar substitutes

"Is glucose a sugar? Yes. Is fructose a sugar? Yes. Are they the same? Not even close." —Peter Attia

Read Time 16 minutes

In this “Ask Me Anything” (AMA) episode, Peter and Bob talk all about sugar and sugar substitutes and provide a way to think about sugar consumption. The conversation begins by defining the various forms of sugar, delineating between added sugar and naturally occurring sugar, and describing the important variables that determine the potential for metabolic damage from consumption. They then take a dive deep into three main categories of sugar substitutes—non-nutritive sweeteners, alcohol sugars, and leaving allulose, in a class by itself—including the safety profile of each, impact on blood sugar and insulin, side-effects, taste preferences, and more. 

If you’re not a subscriber and listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or on our website at the AMA #18 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

  • Delineating the various forms of “sugar” (2:00);
  • Added sugar vs. naturally occurring sugar (12:30);
  • Important variables related to sugar consumption: Density, volume, and velocity (17:00);
  • Alternatives to sugar: Non-nutritive sweeteners (22:30);
  • Alternatives to sugar: Alcohol sugars (34:15);
  • Alternatives to sugar: Allulose (39:00);
  • Contextualizing risk when it comes to sugar substitutes (45:00);
  • Why some people report feeling better when eliminating non-nutritive sweeteners from their diet (46:30);
  • The impact of sweetness—Cephalic insulin response and the metabolic drive to eat more (49:45); and
  • More.


Delineating the various forms of “sugar” [2:00]

Peter’s Sunday email on sugar, allulose, and other sugar substitutes

Peter’s Sunday email about diet soda


Clarifying the nomenclature around the term “sugar” 

  • Peter says he’s frustrated by the use of the term “sugar” 
  • It means a lot of different things, and all of those things can be true. 
  • For example, Glucose is a sugar. Galactose is a sugar. Fructose is a sugar. Sucrose is a sugar. Allulose is a sugar.
  • Rather, Peter prefers to think about these things through the lens of molecules and their basic attributes and not through the most generic nomenclature of their existence

Glucose and fructose

  • Glucose and fructose are monomers — they form the simplest building blocks of carbohydrates
  • They even have the same chemical formula — same number of carbons, hydrogens, and oxygen (C6—six carbons, H12—12 hydrogens, O6—six oxygens)
  • The difference is glucose is arranged in a six carbon ring, whereas fructose is arranged in a five carbon ring (and one of those carbons hangs outside the balance)
  • This seemingly small difference “makes all the difference in the world”

“All things equal, if you just have humans or mice or dogs or camels and force fed them glucose or fructose to their heart’s content, even though they’re the same chemical formula and very similar chemical structure, they would have dramatically different metabolic effects.” —Peter Attia

Figure 1. Glucose and fructose structures. [source]

⇒ See podcasts with Rob Lustig and Rick Johnson  

Some differences

  • First of all, we rarely consume fructose by itself, and we very often consume glucose by itself
  • A bowl of rice or pasta breaks down from more complex starches into simple monomers of glucose
  • Whereas when you consume things that are sweet tasting — those foods contain fructose combined with a dose of glucose as well (e.g., an apple, some honey)
  • As a general rule, the sweeter it is, the more fructose

“Is glucose a sugar? Yes. Is fructose a sugar? Yes. Are they the same? Not even close.” —Peter Attia

Sucrose and HFCS

  • Sucrose is one molecule of glucose and one molecule of fructose put together, covalently, giving you what’s called a disaccharide
  • The easiest example of where sucrose exists is refined sugar out of things like canes and beets

Figure 2. Structure of sucrose. [source]

Introduction of high fructose corn syrup (HFCS):

  • Around the 1970s, tariffs were added to sugar and then we introduced high fructose corn syrup
  • And people sort of thought of fructose is almost like a health food
    • People would say honey, for example, was okay for diabetics because fructose doesn’t stimulate insulin secretion the way that glucose does
  • At its conception, there was a really big spike in HFCS
  • New technology turned sucrose into a solution (HFCS)– 
    • the structure was changed to 45/55 in favor of fructose, so that made it a little sweeter
    • You could produce HFCS in unlimited quantities, solving a big problem for food manufacturers

Current thinking by the public on fructose and HFCS

  • There probably still is a belief that fructose is better for someone with diabetes because you don’t have to chase it with insulin (notwithstanding the fact that fructose does so much for insulin resistance)
    • A topic covered exquisitely by both Rob and Rick
  • Even so, there’s been a little bit of a revolt against HFCS
  • The irony, however, is the belief that things that are more “natural” like dried mangoes and dates and “healthy”, as well as the belief that sucrose is any better for you than HFCS

{end of show notes preview}

Would you like access to extensive show notes and references for this podcast (and more)?

Check out this post to see an example of what the substantial show notes look like. Become a member today to get access.

Become a Member

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user's own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.


  1. Thank you for a Great AMA,I had however hoped that you would have also tested Kabocha Extract, “BochaSweet”, and given your opinion on it. It is a great tasting sweetener that cooks and bakes like sugar, and it doesn’t cause me digestive issues like Allulose. So if you ever have the time please look into it. Thank you once more for your awesome content, I have been a fan for years. Greetings from a not so snowy Finland, Maria

  2. Growing up as an overweight kid in the 80’s, I thought I might help out with some of the finer points of sugar substitute history. First, while Tab was certainly targeted towards women, one of its most memorable devotees was none other than “Pumping Iron’s” own Arnold Schwarzenegger. Rumor had it that when he went on a pleasure cruise in the 80’s, Tab was not on the menu and he made sure that the ship was loaded up with Tab before he would go. To this day, some people love Tab for its metallic aftertaste. Tab was originally sweetened with cyclamate and saccharin. When cyclamate was banned by the FDA in 1969, Tab was forced to reformulate to use 100% saccharin. The most recent iteration of Tab is sweetened with a combination of saccharin and aspartame.

    Sadly, the Coca-cola Company announced that Tab would be discontinued in October of this year. Worse, they also discontinued Diet Feisty Cherry Coke, my favorite soft drink. I have one left and am looking for the right occasion to drink it.

    In 1977, a Canadian study showed that rats fed the equivalent of 800 cans of diet soda a day of saccharin developed bladder tumors compared to the control group. Canada quickly decided to ban saccharin. The FDA moved to do the same, but panic erupted in the US. People began to horde diet sodas. The outcry was so great that congress passed a law in 1977 preventing the US government from banning saccharin. That law is still on the books today. In 1981, saccharin made the NIH’s carcinogen list and packets of Sweet n’ Low had to carry a cancer warning.

    The cancer warning created an opening for aspartame. Aspartame was approved by the FDA in 1981 (mentioned above, but it was not the earliest) and it did not have to carry the warning label that Sweet n’ Low did, making Equal appear to be the “safe” alternative to the carcinogenic Sweet n’ Low. The fact that we refer to Sweet n’ Low as the “pink packet” was, in fact part of Equal’s branding strategy. Rather than referring to Sweet ‘n Low by its trade name, in Equal’s commercials, they referred to it as “the pink packets.”

    Diet Coke launched in 1982… before aspartame was approved as a soft drink sweetener, so it launched with a saccharin formulation. The folks at Coca-cola were aware of aspartame, but they didn’t want to wait on approval. In 1985, Diet Coke would reformulate to aspartame. By the end of 1985 aspartame sales more than doubled saccharin sales.

    in December of 2000, the saccharin came off of the National Toxicology Program’s list of carcinogen’s and Bill Clinton signed a law that did away with warning labels for products containing saccharin. Of course, the damage had already been done as many of the newer sweeteners had already been approved: ace K (1998 for soft drinks, 2003 for general use), sucralose (1998 for some foods, 1999 for general use), neotame (certain uses, 2002), stevia (GRAS notice first filed 2008), monk fruit extract (GRAS notice first filed 2010), advantame (certain uses, 2014).

    I should make one more note that was not mentioned in the podcast. You can’t bake with aspartame as heat will cause it to devolve into its constituent compounds, aspartic acid and phenylalanine.


  3. Great AMA, just one little thing to add regarding the naturals sugars…….Honey and Maple Syrup…….maybe you can go deeper on those 2.

  4. I understand the allulose seems to be safe and have health benefits associated with lowered blood sugar. Is there any literature that actually measures whether allulose provokes an insulin response or do we simply infer that it does not because assume the glucose removal is from the kidneys and not insulin?

  5. Great information that needs to be out in the public, might I even make a case for this being put onto the public feed for everyone.

    Something I’d like to know and sometimes struggles with understanding is the things used to cut these with or additives they use to make it a 1:1 sugar substitute.

    Thank you Peter and the team.

  6. Bought Allulose, major issue with it it doesn’t seem to have the same dissolve properties. It simply needs higher temperatures to dissolve in lets say chocolate. In tea and coffee it simply collects on the bottom.

  7. Hei,

    Thank You for Your great podcast again! Your site has totally changed my view on smoothies. Before I really didn’t care that much what I was putting inside. Now I reserve smoothies for workout days and make them mostly from vegetables, and adding one fruit/wild frozen berries for taste. I still think they are beneficial for bowel healthy if consumed wisely.

  8. “A couple of papers out there that have actually postulated that things like aspartame or other non-nutritive sweeteners can disrupt the gut biome: Saccharin, sucralose, stevia have been studied to alter gut microbiota” I would like to suggest a deep dive into the topic of non-nutrivtive sweeteners and the microbiome including amount and frequency of ingestion and strategies to mitigate impact if consumed in “small amounts”. Thank you.

Facebook icon Twitter icon Instagram icon Pinterest icon Google+ icon YouTube icon LinkedIn icon Contact icon