Check Part 1 HERE and Part 2 HERE

Implications and practical applications of calorie restriction and intermittent fasting

And now … can the practice of calorie restriction (CR) or fasting have therapeutic value in humans? As noted earlier (Part 1), randomized controlled trials in humans studying the effects of CR and fasting in humans are scarcer. It is not easy to find volunteers to subject themselves to the “discomfort” of eating less food.

Just an aside …
Changing something in someone’s diet can be a daunting task! In fact, and based on my experience, people are generally highly resistant to changing whatever their eating patterns are and tend to defend them tooth and nail! They elaborate the most varied rationales (and very sophisticated sometimes … like the typical “but my grandfather is 90 years old and always ate this and that”) to justify the intake of certain foods that, essentially, they are just used to or like eating. Nutrition is like a religion for some, believe me …!

Back to human studies …
The other practical reason for the lack of controlled randomized human trials on the effects of CR or fasting to study its effects on life expectancy and the incidence of “age-related diseases” is that human life expectancy is long. However, some randomized controlled trials in humans point to clear benefits of CR practice in certain populations. Listed below are some of these studies, type of intervention and significant effects observed.

• Wang et al. (2013)

  • Sample: obese individuals.
  • Intervention: 5 days of 30% CR (low-fat / high-carb or high-fat / low-carb) after isocaloric diet period.
  • Significant results:
    • CR diets decreased fasting insulin and leptin levels by increasing free fatty acid levels (indicating mobilization of fat stores);
    • Insulin sensitivity did not improve significantly (perhaps due to the short 5-day period), however muscle insulin signaling (in response to insulin) increased only in the low-fat / high-carb diet subjects. Note that this effect on insulin signaling in response to the low-fat / high-carb diet (rather than the high-fat / low-carb diet) may represent only a transient adaptive response due to the higher glycemic load in the diet. The short duration of the study does not allow the conclusion of a sustained improvement in insulin regulation.
  • Kitzman et al. (2016)
    • Sample: elderly obese individuals (67 ± 5 years) with heart failure.
    • Intervention: 20 weeks of CR (350-400kcal / day deficit) with or without exercise (1 hour walking 3 days per week).
    • Significant results:
      • Both CR and exercise (separately) increased aerobic capacity (indicated by increase in VO2 peak), with even greater effects if combined;
      • Both CR and exercise (separately) improved body composition (fat loss) with even greater effects if combined;
      • CR (but not exercise) reduced the inflammatory marker C-reactive protein (CRP) and correlated with weight loss.
  • Snel et al. (2012)
    • Sample: obese individuals with type 2 diabetes mellitus (T2DM) and insulin-dependent.
    • Intervention: 16 weeks of CR (450kcal / day) with or without exercise (1 hour + 4 30-minute sessions on a cycle ergometer per week).
    • Significant results:
      • Both CR and exercise improved fasting glucose, insulin and glycosylated hemoglobin (HbA1c) levels;
      • The RC + exercise group lost more fat and waist circumference compared to the CR group only;
      • Both CR and exercise increased insulin receptor expression and signaling (revealed by muscle biopsy) as well as peripheral insulin sensitivity.
  • Pedersen et al. (2015)
    • Sample: overweight or obese, non-diabetic individuals with coronary artery disease.
    • Intervention: 12 weeks of CR (800-1000kcal / day) with or without exercise (3 days / week interval aerobic sled).
    • Significant results:
      • Separately, CR was superior to exercise in weight loss, fat mass and waist circumference, as well as fasting blood glucose, insulin sensitivity and glucose tolerance. However, CR led to better results combined with the exercise program.
  • Razny et al. (2015)
    • Sample: non-diabetic obese individuals
      Intervention: 3 months CR (1200-1500 kcal / day) with or without 1.8 g / day omega-3 fatty acids (in a 5: 1 DHA / EPA ratio).
    • Significant results:
      • CR with or without omega-3 supplementation resulted in similar decrease in body weight and fat mass;
      • CR had a superior positive effect on triglyceride and insulin levels when combined with omega-3 supplementation;

RC + omega-3 (but not only CR) improved indicators of insulin resistance (HOMA index).

  • Prehn et al. (2016)
    • Sample: postmenopausal obese women.
    • Intervention: 12 weeks CR (<800kcal / day) followed by 4 weeks on an isocaloric diet or 16 weeks on an isocaloric diet (control group). Recommendation to increase physical activity per week.
    • Significant results:
      • CR (but not the isocaloric diet) resulted in better scores on memory performance tests;
        CR (but not the isocaloric diet) resulted in improved glycemic control and HbA1c levels;
      • CR-induced increase in cerebral gray matter density was negatively correlated with glucose levels.

Recommendations and Conclusions

In fact, CR or fasting interventions do indeed appear to have clear therapeutic utility in improving health parameters related to obesity, inflammation, insulin resistance, oxidative stress, and cardiac function. It is important to note that just reducing the amount of food you eat may not be enough and perhaps not recommended. Such a simplistic and long-term intervention can result in nutritional deficits and thereby boycott putative positive health outcomes. It is therefore important to monitor and ensure adequate nutrient levels through supplementation and / or in choosing nutritionally dense foods. Also noteworthy are the positive synergistic effects that CR seems to have when combined with exercise (Snel et al., 2012; de Luis et al., 2015; Kitzman et al., 2016), which may be prescribed concomitantly. In this context, a very mild CR intervention (e.g. 10% deficit) or short intermittent fasting periods (> 14 hours and does not need to be daily) combined with exercise may have very positive effects and are likely to have higher compliance compered to more aggressive fasting or CR interventions.

Of course, severe and prolonged CR with no exercise (especially strength training) can induce lean mass loss that is highly undesirable if the goal is to improve health. Once again, and as with almost everything, the secret lies in the right dosage! In certain populations such as pregnant women (or women trying to conceive) and young growing individuals, prolonged CR interventions should be avoided as they may compromise development. However, I emphasize again that the most important thing is not to ingest “calories” but ingest “nutrients”! In older individuals with sarcopenia, CR should perhaps be avoided, although the most determining factors for reversing sarcopenia are strength training and adequate protein intake (which should be higher for older individuals (> 2g / kg bodyweight).

Regarding the specific case of intermittent fasting (note: the focus of this article is not to discuss the use of intermittent fasting as a fat loss and / or maintenance strategy or muscle mass gains in the sports context, but rather its potential for general health benefits) although few, the available randomized controlled trials in humans indicate that intermittent fasting do offer beneficial effects similar to those of constant CR and perhaps is easier to implement (Donati et al., 2008; Marzetti et al., 2009; Alirezaei et al., 2010; Arum et al.; 2014; Godar et al., 2015). Irregular fasting episodes (e.g. not eating breakfast once or twice a week on non-training days) can not only be a strategy easy to implement strategy as a mean to control total weekly calories ingested, and it also has positive hormonal effects is mediated by some of the mechanisms described above. “Hormesis” is defined as a mild stressor that is beneficial to health, stress resistance, growth and longevity. It results from exposure to an “adequate” dose of a stressor. CR or fasting (or exercise) is something that we are evolutionarily designed to tolerate, and which at the right dose gives us benefits and greater resilience. The occasional stress of not eating can be a “healthy discomfort”!

Until next time!

Nuno Correia