Note: This article was originally published in July 2019

Scientists have extended the life spans of lab animals by cutting 10-40% of their normal daily calorie intake.

And this kind of caloric restriction also reduces experimental animals’ risks for cancer and other age-related diseases.

We still don’t know whether this kind of calorie restriction can extend human life spans — but exciting new findings from a Duke Health clinical trial suggest that modest calorie-cutting brings significant health benefits.

Four years ago, we summarized the results of a two-year clinical trial involving 218 participants (70% women), of healthy weight or slightly overweight some of whom cut their daily calorie intake by one-quarter (25%).

As we reported in Calorie Cutting May Make for Better Sleep, Sex & Moods, the calorie-restriction group in that trial lost an average of 16.7 pounds, compared with less than one pound in the control group.

And, compared with the control group, the calorie-restriction group reported improved sleep at year one, and higher energy levels, better mood, stronger sex drive, less tension, and improved general health after two years — with no adverse side effects.

Now, the results of another trial of similar size and length suggest that dropping just 300 calories a day reduces cholesterol and inflammation levels and the consequent risk for diabetes and heart disease.

In fact, as the study’s lead author told The New York Times, “We weren’t surprised that there were [beneficial] changes. But the magnitude was rather astounding. In a disease population [i.e., people less healthy than the study participants], there aren’t five drugs in combination that would cause this aggregate [total] of an improvement.”

Duke Health study sees big benefits from modest calorie-cutting

The Duke Health trial was part of an ongoing collaborative project with the National Institutes of Health, called CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy).

The new two-year clinical trial involved 238 healthy adults aged 21 to 50 years who were lean or slightly overweight (Kraus WE et al. 2019).

It was the first major clinical trial to test the effects of calorie-cutting in generally healthy middle-aged or younger adults of normal weight or who were slightly overweight.

And its findings support the Duke researchers’ hypothesis that the metabolic changes triggered by eating fewer calories than we burn — which predictably produces weight loss — also significantly improves blood cholesterol, inflammation, and sugar (glucose) levels.

The 143 participants assigned to the calorie-cutting group were provided plans for three daily meals that reduced their normal calorie intake by one-quarter (25%).

For the first six months, the calorie-cutting group also attended intensive group and individual counseling sessions, and took lessons in low-calorie cooking.

To make calorie-cutting easier, each participant could select from one of six different — and flexible — meal plans designed to accommodate cultural preferences or other needs (e.g., gluten-free).

In contrast, the 75 participants assigned to the control group continued to consume their normal diets and met with researchers once every six months.

Perhaps in response to the low-calorie cooking training, the calorie-cutting group didn’t end up reducing their protein intake, but they ate significantly less fat and slightly fewer carbohydrates. Per gram, fat contains twice as many calories (9) as protein or carbohydrates (4).

The fact that the members of the calorie-cutting group also consumed more vitamins and minerals — as revealed by regular blood tests — suggested that they had raised their intakes of fruits and vegetables, probably due to the training in low-calorie meal preparation, which emphasized fresh, filling, whole foods.

Unsurprisingly, the volunteers assigned to the calorie-cutting group varied in their ability to maintain a 25% cut in their normal calorie intake, so the average daily reduction in calories ended up being about 12% — about 300 fewer calories per day.

As a consequence, the people in the calorie-cutting group lost 10% of their body weight — 71% of which was fat — and maintained that 10% loss over the course of the two-year trial.

After two years, the 143 members of the calorie-cutting group also enjoyed significant improvements in these health markers:

  • Insulin-sensitivity index
  • Metabolic syndrome score
  • LDL-cholesterol, total cholesterol to HDL-cholesterol ratio, and blood pressure (systolic and diastolic).
  • Blood levels of C-reactive protein, and inflammation marker linked to heart disease, cancer, and cognitive decline.

“There’s something about caloric restriction, some mechanism we don’t yet understand that results in these improvements,” said the study’s lead author, cardiologist and professor of medicine William E. Kraus, M.D.

Dr. Kraus expressed the positive outcomes in plain English: “This shows that even a modification that is not as severe as what we used in this study could reduce the burden of diabetes and cardiovascular disease that we have in this country.”

And, as he said, “People can do this fairly easily by simply watching their little indiscretions here and there, or maybe reducing the amount of them, like not snacking after dinner.”

He pointed out that 300 is the number of calories you’d get from eating six Oreo cookies, which is a smaller sacrifice than many might assume.

(For a sense of which combinations and portions of foods constitute 300 calories, visit the BBC blog post titled "300 calorie meal recipes", which also serves as a good guide to how to build a daily diet with fewer calories. We also recommend taking a look at "10 ways to cut 500 calories a day" from the U.S. National Library of Medicine.)

As Dr. Kraus said, they also want to find the root reasons behind the metabolic benefits of calorie restriction: “We’ve collected blood, muscle and other samples from these participants and will continue to explore what this metabolic signal or magic molecule might be.”

The study authors came to encouraging conclusions: “These findings suggest the potential for a substantial advantage for cardiovascular health of practicing moderate calorie restriction in young and middle-aged healthy individuals, and they offer promise for pronounced long-term population health benefits.”

Modest calorie-cutting proved bearable over time

While, compared with the control group, more people in the calorie-cutting group dropped out of the study, the “retention rate” was quite high.

In addition, the calorie-cutting group reported enjoying better sleep, more energy and improved overall mood.

And, compared to the control group, the test group didn’t report significantly more food cravings for hunger.

Interestingly, the results of a trial published two years ago suggest that it’s harder to achieve calorie-cutting by fasting every other day than by cutting your daily calorie intake (Trepanowski JF et al. 2017).

And the results of a small 2005 clinical trial suggest that an “eat-the-right-foods” focus works as well or better for weight loss than calorie-cutting, at least for the first three months. For more on that, see Fish-Friendly Low-Carb Diet Beats Calorie-Cutting.


  • Kraus WE, Bhapkar M, Huffman KM, Pieper CF, Krupa Das S, Redman LM, Villareal DT, Rochon J, Roberts SB, Ravussin E, Holloszy JO, Fontana L; CALERIE Investigators. 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Jul 11. pii: S2213-8587(19)30151-2. doi: 10.1016/S2213-8587(19)30151-2. [Epub ahead of print]
  • Maki KC, Rains TM, Kaden VN, Quinn J, Davidson MH. A randomized, controlled clinical trial to evaluate the efficacy of a modified carbohydrate diet for reducing body weight and fat in overweight and obese men and women. Session#: 448, Program/Abstract # 448.5, April 3, 2005. Experimental Biology 2005. 
  • Trepanowski JF, Kroeger CM, Barnosky A, Klempel MC, Bhutani S, Hoddy KK, Gabel K, Freels S, Rigdon J, Rood J, Ravussin E, Varady KA. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jul 1;177(7):930-938. doi: 10.1001/jamainternmed.2017.0936.