The Ultimate Guide to Sugar and Sweeteners

This article is a summary of the AMA Podcast by Peter Attia: #361 – AMA #74: Sugar and sugar substitutes: weight control, metabolic effects, and health trade-offs


Sugar is one of the most common questions I get, whether in the gym or out and about. Should I avoid it completely? Are artificial sweeteners better or worse? What about “natural” sugars like honey or maple syrup?

I also frequently hear incorrect advice or 20-year-old dogma that has been proven wrong many times, but the info still hasn’t made it to the general population.

The truth is, sugar and sugar substitutes are a daily decision point for nearly everyone. This guide is built to cut through the noise and provide a framework you can actually apply.

We’ll cover:

• Why we crave sugar.

• How sugar impacts appetite, weight, and metabolic health.

• Natural vs. refined sugar.

• Why timing matters as much as quantity.

• The good, bad, and surprising truths about sugar substitutes.

• Long-term safety concerns (cancer, cardiovascular disease).

• How to make real-world choices for drinks, protein products, and desserts.

Why We Crave Sweetness

Humans are hardwired to love sugar. For most of our history, starvation, not obesity, was the bigger threat. Sweetness signaled quick, safe energy and guided us away from bitter, potentially toxic foods.

That wiring hasn’t changed, even though our food environment has. Our genome still drives us toward sweetness, even though today’s problem is overabundance, not scarcity.

Bottom line: if you crave sugar, it’s not weakness. It’s biology.

Sugar and Health – The Big Questions

Is Sugar Uniquely Harmful?

In strictly controlled conditions, sugar isn’t more fattening than other carbs if calories are equal. But here’s the problem: life isn’t a metabolic ward.

Sugar has a unique ability to:

• Increase appetite.

• Spike and crash energy levels.

• Lead to overeating.

• Reduce satiety compared to fats and proteins.

That’s why, in the real world, sugar often leads to weight gain.

Why Sugar Drives Appetite

• Carbs are less filling than fat or protein.

• Sugar digests quickly, spikes insulin, then drops glucose—leaving you hungry again.

• Sugar also lights up brain reward pathways, encouraging eating beyond hunger.

This explains why you can plow through a bag of gummy bears even if you’re full.

Types of Sugar and Their Impact

• Glucose: signals satiety, replenishes glycogen.

• Fructose: doesn’t trigger satiety hormones as effectively, depletes cellular energy quickly, and pushes you to eat more.

• Sucrose: table sugar, a 50/50 mix of glucose and fructose.

• High Fructose Corn Syrup (HFCS): similar to sucrose but sometimes higher in fructose.

Form matters:

• Liquids (soda, juice) = fastest absorption, biggest appetite driver.

• Solids with fat/fiber (chocolate, fruit) = slower absorption, less disruptive.

• Whole foods (fruit, veggies) = naturally buffered with fiber, water, micronutrients.

Natural vs. Refined

Biochemically, sugar is sugar. Cane sugar, HFCS, honey, or agave all break down into the same molecules. “Natural” sweeteners often carry even higher fructose loads than refined sugar.

Unless it’s in whole food form (an apple vs. apple syrup), “natural” doesn’t mean healthier.

Does Timing Matter?

Yes. Sugar’s impact depends on your body’s ability to handle glucose.

• Best time: after exercise, when insulin sensitivity is high and muscles are eager to store glycogen.

• Worst time: late at night, when insulin sensitivity is lower, glucose spikes are higher, and clearance is slower.

Sugar in Practice: Tailoring to Health

Sugar tolerance varies widely.

• For those with insulin resistance or fatty liver disease, carbohydrate tolerance is low, and sugar should be minimized.

• For metabolically healthy, active individuals, sugar can be tolerated in larger amounts, especially around workouts.

As with most things, context matters more than absolutes.

Sugar Substitutes: The Good, Bad, and Misunderstood

Categories

1. Synthetic sweeteners: Aspartame, sucralose, saccharin.

2. Naturally derived: Stevia, monk fruit.

3. Sugar alcohols: Xylitol, erythritol, sorbitol.

4. Rare sugars: Allulose.

The Big Three

Aspartame, sucralose, and saccharin are incredibly sweet, virtually calorie-free, and heavily studied. Evidence suggests they’re not dangerous in regular doses, but they tend to have slight adverse effects on metabolic health.

Weight Control

Switching from Coke to Diet Coke? It’s a step up, but not a silver bullet. Studies show diet soda is usually weight-neutral because the body compensates by eating more calories elsewhere.

Switching from Coke to soda water? That’s where meaningful weight loss happens.

Glycemic Control & Microbiome

Some studies suggest sugar substitutes can worsen glycemic control and disrupt the gut microbiome. But the effect depends heavily on diet quality. A diet rich in fiber and whole foods blunts the downside.

Use Cases

1. Beverages: Diet soda is better than regular soda, but sparkling water is best.

2. Protein products: Small amounts of sweeteners in protein bars or powders are worth it if it helps you hit protein targets.

3. Desserts: Using artificial sweeteners to satisfy cravings often backfires. They don’t signal satiety the way sugar does, leading to more overeating.

Spotlight on Specific Sweeteners

Allulose - The Standout

• ~70% as sweet as sugar, but only 0.2 kcal/g.

• Activates the same satiety signals as sugar (SGLT1).

• Slows glucose absorption, improves glycemic control.

• Promising for weight and diabetes management, though more human trials are needed.

• Limitation: poor shelf life, making it hard to use in packaged foods.

Best use: in home recipes or fresh-made products.

Stevia, Monk Fruit, and Sugar Alcohols

• Slightly positive effects compared to sugar.

• Not dramatic, but better than aspartame or sucralose.

• Sugar alcohols: fewer calories, lower glycemic impact, but often cause GI issues.

  • Erythritol: gentlest.

  • Xylitol: helps dental health, especially in gum.

  • Sorbitol: most likely to cause GI distress.

Long-Term Safety

Cancer

No credible evidence links sugar substitutes to cancer at real-world doses. WHO’s aspartame warning was based on flawed animal studies at absurdly high intake levels.

Cardiovascular Disease

Recent headlines tying sugar alcohols to heart disease were based on weak science. Higher blood levels of erythritol and xylitol are more likely markers of underlying disease, not causes. No solid evidence shows dietary intake raises risk.

Why the Scary Headlines?

• Bias toward “natural is good, artificial is bad.”

• Media oversimplification.

• Social media amplification.

The reality is more nuanced: dose, context, and overall diet matter far more.

Practical Framework

Here’s the harm spectrum for sweeteners:

• Beverages: Coke → worst. Diet Coke → better. Sparkling water → best.

• Protein products: Sweeteners are worth it if they help you hit your protein needs.

• Desserts: Better to have a small portion of the real thing or fruit.

Rule of thumb:

• Best evidence: Allulose.

• Good: Stevia, monk fruit, sugar alcohols.

• Neutral to slightly negative: Aspartame, sucralose, saccharin.

• Gold standard: whole fruit.

Conclusion

Sugar itself isn’t toxic. But the form, timing, and context determine its impact. Artificial sweeteners can be useful tools, but they’re not magic.

The practical goal is simple:

• Move from sugar → artificial sweeteners → minimal added sweeteners.

• Use fruit as the primary way to satisfy a sweet tooth.

• Keep diet sodas occasional, not daily staples.

With this framework, you can make smarter choices about sugar that align with your goals, whether that’s better health, weight control, or just feeling better day to day.