Fasting VS Dieting (Calorie Restriction): New Study Seeks to Find out Which Approach is Best for Fat Loss, Longevity

by Mike Mutzel


Benefits of calorie restriction depend on fasting window, new study finds.



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Video Time Stamps:

0:00 Intro
0:05 Shared Features of Fasting and Calorie Restriction
0:23 New Study
1:23 Big Omission from Calorie Restriction Data
2:40 Blood Work MasterClass
3:53 Testing Fasting VS Calorie Restriction study details
6:40 Fuel Switch with fasting
7:23 Insulin, Glucagon and fat oxidation
08:54 Metabolic profiling of different fasting patterns
10:38 Experiment Number 2
11:03 Lifespan extension in fasting VS CR VS Ad Lib
13:43 Match Carbohydrate intake with exercise
14:10 TRF Feeding pattern practical tips

Fasting VS CR: New study seeks to find out what mechanism is at work:

It’s common knowledge that calorie restriction is a validated strategy to extend lifespan and delay the onset of age-associated diseases. But there’s a new wrinkle that’s muddied the waters of this calorie restriction (CR) research, which, needless to say, has up to now been derived mainly from studies conducted in rodents (animal models).

In laboratory settings, animals are both calorie-restricted and their feeding windows are also compressed—feeding for just 2 hours and fasting for the other 22. This realization complicates CR research as far as understanding what mechanism is linked to the benefits: the calorie restriction (CR), the extended daily fast, or both?

To help disentangle these questions, scientists at the University of Wisconsin randomized animals to one of four different feeding patterns:

1. Ad libitum access to food (no CR)
2. Ad libitum access to a 30% calorie-restricted diet (no feeding window compression)
3. 30% calorie-restricted feeding using an automatic feeder that released food at three different intervals during mice’s 12-hour dark (feeding period); that is TRF + CR
4. 30% calorie-restricted diet; fed just once per day in the morning causing a prolonged fast, which is essentially an OMAD with CR

How Different Fasting Schedules and Calorie-Restriction Regimes Impact Physiology

Mice, in all feeding patterns where calories were restricted, had a decrease in energy expenditure (as expected). The mice in the classic calorie-restricted (CR + OMAD) diet and time-restricted feeding (TRF + CR) had improvements in body composition, glucose tolerance and insulin sensitivity, suggesting prolonged fasting is necessary to achieve these desired effects.

To assess the additional impact of fasting paired with calorie restriction and how it impacted fatty acid oxidation, a metabolic chamber was used to evaluate respiratory quotient. It was discovered that CR + OMAD mice and TRF + CR mice had nearly indistinguishable patterns of increased fuel switching during the fasting period; that is, an increase in fatty acid oxidation that was not observed in the ad libitum fed mice.

Using gene transcriptome profiles, the scientists identified 2,700 genes in the liver and 1,800 genes in fat tissue that were expressed differently in the CR + OMAD and CR + TRF mice relative to the ad libitum control mice. As one might expect, due to the added fat loss in the animals subjected to compressed feeding windows, more metabolic pathways were altered in white fat tissue than in the liver.

Six key metabolic pathways were enriched in both tissues in the combined calorie-restricted and compressed feeding window-fed mice, including insulin signaling, PPAR signaling, and circadian rhythm as well as fatty acid metabolism and biosynthesis pathways.

However, there were two important pathways that were upregulated in the fat and liver of the TR+ CR fed mice (not the OMAD + CR fed mice): TGF-beta signaling pathway and longevity-regulating pathway. To be fair, I don’t fully understand exactly this pathway, does but it sounds cool! (Insert smiley face emoticon here.)

Lastly, the researchers analyzed how lifespan was impacted by three different feeding patterns (ad lib gorging, ad lib CR and CR OMAD). The CR + OMAD feeding pattern extended lifespan by about 20% to 1,022 days VS 850 days for the ad lib-fed mice. The CR + OMAD also was associated with lower frailty indexes, less distended abdomen and better maintenance of coat and fur color over 24 months compared to ad lib fed mice.

In closing, fasting is a necessary element for calorie restriction to improve insulin sensitivity, create the metabolic switch to increase fatty acid oxidation (reducing fat mass) and reduce age-related frailty. That said, this study found that calorie restriction without any feeding window compression still improves glucose tolerance and leads to favorable changes in body composition.

So if you’re striving to achieve metabolic improvements and molecular effects associated with longevity linked with calorie restriction, recognize that the health benefits are shared and overlapping with fasting. A two-pronged approach (i.e., fasting and or TRF paired with mild calorie restriction will help you actualize these benefits faster.


Pak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., et al. (2021). Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice. Nature metabolism, 3(10), 1327–1341.

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