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;
- Sample: non-diabetic obese individuals
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.
- CR (but not the isocaloric diet) resulted in better scores on memory performance tests;
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
CAN CALORIE RESTRICTION OR INTERMITTENT FASTING HELP PREVENT “AGE-RELATED DISEASES” AND LIVE LONGER? – PART 1
Introduction
In this article I will look into the possibility of calorie restriction or intermittent fasting, which is just an alternative strategy to induce a caloric deficit, effective nutritional therapeutic strategies to prevent, alleviate or even eliminate some of the so-called “age-related diseases”, thus contributing for a better and longer life. It is important to note that most studies on the effects of calorie restriction or intermittent fasting (or intermittent calorie restriction) on life expectancy are mechanistic, and conducted in animal and / or in vitro models. It is understandable that there are fewer human intervention studies in this area. If we think about it, it is not easy to conduct studies with humans on calorie restriction to study its effects on life expectancy and the incidence of “age-related diseases”. Not only it is not easy to recruit people to voluntarily incur in a calorie restriction period, it is also not practical to study in humans (in a randomized controlled manner) the effects of calorie restriction or fasting on life expectancy, because they simply “live a long time”. ” In order to obtain timely results, it is essential to conduct studies on species with a shorter life expectancy. However, observational studies and some human intervention studies (discussed later) appear to confirm the same health benefits and molecular mechanisms as those observed in animals.
It should also be noted that, in the experimental context, caloric restriction is defined as “reduced food intake without malnutrition”. In other words, nutritional interventions imply a 10-40% reduction in daily caloric requirements in which only calories, and not nutrients, are restricted (in most controlled studies this is ensured with vitamin and mineral supplementation) (Kitada & Koya, 2013b; Robertson & Mitchell, 2013). This notion is important! Caloric deficit does not imply nutrient deficit and caloric surplus does not imply that nutrient requirements are met. Intermittent fasting will be no more than an alternative method of calorie restriction in which food intake is restricted for a certain period of time (usually 16 to 24 hours) followed by an unrestricted intake period and has been touted as producing beneficial health effects similar to more constant calorie restriction protocols (Martin, Mattson, & Maudsley, 2006; Robertson & Mitchell 2013).
Part 1
Should we accept being “sick” just because we get older?
It is recurrent to hear that the disease is something that “comes with the age package.” In fact, getting older is a drag! The general perception of a progressive decline of all our capabilities as we age is, unfortunately, not an illusion. There are several theories about aging. While certainly a very interesting topic, a detailed description of the various theories of aging is not the purpose of this article. These are some of mechanisms underlying the aging process which are generally pointed out as the main ones:
- The “Hayflick limit” (phenomenon discovered by Leonard Hayflick) determines that human cells have a replication limit number, after which they become senescent. Telomeres (i.e. a kind of protective “helmets” at the end of each chromosome) become progressively shorter with each cell division (Shay & Wright 2000). However, DNA methylation (an essential and repairing process consisting of the addition of methyl groups to DNA and which can be promoted by the abundance of dietary methyl donors for example) is said to be protective of telomere length and that way to postpone cell death and aging. For example, in animal models, hypomethylation of the enzyme telomerase reverse trancriptase has led to the preservation of leukocyte telomere length (Zhang et al. 2003; 2014). In this example, it is plausible to infer that delaying leukocyte senescence (through methylation and consequent telomere length conservation) may contribute to a stronger immune system and thus positively influence longevity.
- This theory suggests that unresolved chronic inflammation induces the human organism not to allocate resources for the functioning of other body functions (as they are permanently allocated to unresolved inflammation) and thus leading to early aging of various organs and tissues, and the early onset of “age-related diseases”.
- This theory, originally proposed by Dr. Denham Harman in 1956, is based on the premise that the aging process is mediated by free radical damage. Theoretically, by reducing free radical accumulation (e.g. reactive oxygen species) and at the same time increasing the antioxidant capacity of the organism (increasing glutathione, and antioxidant enzymes such as SOD and catalase), tissue damage can be prevented (by slowing down aging process) and to prevent the occurrence of “age-related diseases” and consequently contribute to increase functional longevity (Harman, 1988; 2006).
Very well, getting older is inevitable! We already know that. However, if we give it a little thought, all the mechanisms mentioned have an environmental root, that is, we can, to some extent, control them through decisions that we make every day. Namely decisions about what we eat and how we move. And this is good news! It is in fact in our hands to slow down the process of senescence and prevent the onset of the so-called ‘’age-related diseases’’. Note that if for us (Westernized world) it is statistically “normal” to grow old with diabetes, hypertension, cancer, dementia, sarcopenia, osteoporosis, cardiovascular disease, insulin resistance, obesity and chronic inflammation (because the population studied incurs in a lifestyle that leads to disease), in other contemporary (non-Westernized) populations such diseases are rare or even non-existent. In this context, I invite the reader to consult what I consider to be one of the best books I know about nutrition and lifestyle, and its relation to the incidence of so-called “Western” diseases: Food and Western Disease: Health and Nutrition from an Evolutionary Perspective by Staffan Lindeberg. In fact, if we want to aim at maximizing health and lifespan potential, we should not just look at what is ‘’normal’’ in a given population, because that may be a sick population. Rather, we should look for what is “biologically normal” for a human being! A species that is designed (evolutionarily) to deal with a range of environmental stimuli that include certain levels of physical activity, nutrition, sun exposure and sleep. And, although aging is a normal process, it should not be “biologically normal” to age with chronic disease.
In this context, the Okinawa Centenarian Study is also frequently cited. The Okinawan population has the highest ratio of (healthy) centenarians on the planet (50 / 100,000 vs 10-20 / 100,000 in the USA) and as such is of greatest interest to study the factors that potentiate this kind of longevity. One of the factors identified (in addition to an appreciable level of physical activity and social interaction) was the fact that populations over 70 eat about 11% of calories below (about 1785kcal / day, which is a very moderate level of calorie restriction) than would be recommended for maintaining body weight (according to the Harris-Benedict equation), however on a nutrient-rich diet (Wilcox et al., 2006).
What we can do to live longer and better is one of my main interests. As I mentioned, our choices regarding the type of exercise, food we eat and other lifestyle factors can affect how long we live and, perhaps most importantly, how healthy and functional we live. In Part 2 of this article I will discuss some mechanisms by which nutritional interventions such as calorie restriction or intermittent fasting can lead to health benefits. And in Part 3 I will address the possible implications and practical applications of the practice of calorie restriction or fasting, as well as which populations can benefit most from these nutritional strategies and whoshould avoid them.
Stay around!
Nuno Correia
References
Dröge W., 2009. Avoiding the First Cause of Death. New York, Bloomington. iUniverse, Inc.
Harman D., 1988. Free radicals in aging. Mol Cell Biochem. Dec; 84(2), pp.155-161.
Harman D., 2006. Free radical theory of aging: an update: increasing the functional life span. Ann N Y Acad Sci. May;1067, pp.10-21.
Kitada, M. & Koya, D., 2013b. SIRT1 in Type 2 Diabetes: Mechanisms and Therapeutic Potential. Diabetes & metabolism journal, 37(5), pp.315–25.
Lindeberg, S., 2010. Food and Western Disease: Health and Nutrition from an Evolutionary Perspective. Oxford, United Kingdom: Wiley-Blackwell.
Martin, B., Mattson, M.P. & Maudsley, S., 2006. Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing research reviews, 5(3), pp.332–53.
Masoro.E. L., 2002. Caloric Restriction: A Key to Understanding and Modulating Aging. Texas, USA: ELSEVIER.
Robertson, L.T. & Mitchell, J.R., 2013. Benefits of short-term dietary restriction in mammals. Experimental gerontology, 48(10), pp.1043–8.
Shay J.W., Wright W.E. 2000. Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol. Oct;1(1), pp.72-76.
Zhang D. et al., 2013. Homocysteine-related hTERT DNA demethylation contributes to shortened leukocyte telomere length in atherosclerosis. Atherosclerosis. Nov; 231(1), pp.173-179.
Zhang D.H., Wen X.M., Zhang L. & Cui W., 2014. DNA methylation of human telomerase reverse transcriptase associated with leukocyte telomere length shortening in hyperhomocysteinemia-type hypertension in humans and in a rat model. Circ J. 78(8), pp.1915-1923.
Wilcox D.C. et al., 2006. Caloric restriction and human longevity: what can we learn from the Okinawans? Biogerontology 7, pp.173–177.
For many years, breast cancer survivors have been told not to lift anything heavier than a handbag because of the risk of lymphedema (swelling / edema caused by accumulation of lymphatic fluid in the tissues of the body’s surface). This accumulation of lymphatic fluid (lymph) arises as a consequence of changes in the lymphatic system due to surgery and / or radiotherapy to the lymph nodes in the axilla and surrounding areas.
In this regard, it is recommended that women should ask for help with shopping bags, should avoid lifting or carrying children, and should only engage in exercise modalities such as walking, swimming and other light aerobic activities – these are the general recommendations. However, a study published in the New England Journal of Medicine in 2009 (see reference below) has shown that lifting weights can be a substantial aid to women with or at risk of developing arm lymphedema.
In this study the researchers recruited 141 breast cancer survivors with stable arm lymphedema and divided the sample into two groups – one group did strength training and the other did not change their exercise routine. These were the conclusions of the authors of the study: “in breast-cancer survivors with lymphedema, slowly progressive weight lifting had no significant effect on limb swelling and resulted in a decreased incidence of exacerbations of lymphedema, reduced symptoms, and increased strength.”
So, the main question here is not whether women who suffer from this condition may or may not lift weights but HOW they should do it to improve their condition. Again, the critical component is the program design, and this is one of our distinctive competencies at The Strength Clinic.
Train smart.
Pedro Correia
References
Schmitz KH, Ahmed RL, Troxel A, Cheville A, Smith R, Lewis-Grant L, Bryan CJ, Williams-Smith CT, Greene QP. Weight lifting in women with breast-cancer-related lymphedema. N Engl J Med. 2009 Aug 13;361(7):664-73. doi: 10.1056/NEJMoa0810118. PubMed PMID: 19675330.