Meal Frequency Effect on Disease

Intermittent energy restriction and other approaches to timing and frequency of meals may affect well-being.

Obesity,  like other diseases such as cardiovascular disease, cancer, Alzheimer’s and diabetes, is very common in modern society. It is generally combated with a reduction in caloric intake, optimization of body weight and implementation of a balanced diet. Recent findings suggest that not only what you eat, but how much you eat and when you eat it, may have a more important bearing on overall well-being than previously thought.

Historically, hunter-gatherer communities did not eat at regular intervals. Today’s hunter-gatherer arthropods eat based upon availability of food, sometimes only three times per week. This is possible because mammals have retained evolutionary adaptations necessary for intermittent food availability, such as the liver’s ability to store glycogen as well as fatty acid stores in adipose tissue. Wild animals and contemporary hunter-gatherer humans seldom suffer from diabetes, cardiovascular disease or obesity. It’s on this premise that Dr. Mark Mattson and his team hypothesized 3 experimental dietary regimens that may provide health benefits.

The 3 dietary regimens include: a) caloric intake restriction (CR); daily intake reduction by 20-40% with no change in meal frequency, b) intermittent energy restriction (IER); fasting 2 days a week or reducing daily calories to 500, and c) time-restricted feeding (TRF); restricting daily caloric intake to 4-6 hour time windows.

According to Dr. Mattson, 10% of expressed genes in organs exhibit circadian rhythms, which encode rate-determining steps in metabolic pathways. The time of food intake affects the phases of these rhythms in peripheral tissues like the liver, adipose tissue and muscle. Modern society eats at all times of the day and night, such as those individuals that work nightshift, in which there is a known association of cancer, cardiovascular disease, obesity and diabetes. TRF studies have been shown to increase weight loss in obese humans without altering caloric intake or the source of calories. Similarly, TRF has been shown to prevent metabolic diseases in mice models.

Studies on CR and more specifically, IER have been shown to prevent disease in 4 key ways. Bioenergics: Studies have found switching from 3 square meals daily to 500 calories every other day elicits changes in energy metabolism including increased insulin sensitivity, elevation of ketone levels, and reduced levels of insulin and leptin. Adaptive stress responses: IER in animal models has shown increased antioxidants and a protective effect on neurons as well as neurogenesis in Alzheimer’s and Parkinson’s disease. Essentially, by exposing cells to mild stress, they become conditioned to resist greater stress from disease. Inflammation: Fasting lessens inflammation in rheumatoid arthritis and data from animal models suggest other autoimmune disorders like multiple sclerosis, lupus and type I diabetes may be counteracted by IER. However, there are also obvious detrimental effects of reducing the inflammatory response such as suppressed immune response to infection. Removal of damaged organelles: The mTOR pathway is responsible for stimulation of autophagy in the kidney, liver and skeletal muscle. This pathway is stimulated by fasting, which in turn promotes cell clean up.

Due to the heterogeneity of human genetic composition, epigenetics and environmental factors, it’s difficult to generalize the response of cells and organ systems to different eating regimens. Evidence supports the implementation of TRF, IER and CR to improve health of obese patients, but evidence is lacking in people of normal weight. Dr. Mattson does not try to hide the fact that most of the data presented in his paper lack randomized controlled trials in humans. However his findings do raise some interesting questions and suggest that there is a need for RCTs on the subject, specifically with healthy human subjects as well as those suffering from cancer, cardiovascular disease, obesity and diabetes.

Practice Pearls:

• Studies have found 4 mechanisms by which IER protects cells from disease and insult: bioenergetics, adaptive stress responses, prevention of inflammation and improved removal of damaged molecules and organelles.
• There is sufficient evidence that suggests IER and CR can improve the health of obese patients, but there is a lack of data for people of normal weight.
• RCTs should be performed on IER and TRF in healthy as well as diseased human subjects to better understand the associated benefits and risks.

Researched and prepared by Devon Brooks, Doctor of Pharmacy Candidate from LECOM College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE

 

Mattson MP, Allison DB, Fontana L, Et al. “Meal frequency and timing in health and disease.” Proceedings of the National Academy of Sciences of the United States of America. 111.47 (2014):16647-16653. Print.