The effects of calorie restriction on immune function and inflammation
Move over mustache wax, craft beer, and fixed-gear bicycles: fasting is making a comeback.
By no means a new therapy, fasting has its roots in religion and medicine alike. In fact, the Greek physician Hippocrates, who lived from about 460 to 375 BCE, prescribed breaks from eating and drinking for certain health conditions.
In more recent times, fasting and variations thereof – including calorie restriction, intermittent fasting, and other fast-mimicking diets – have been shown to extend life expectancy, reduce inflammation, drop cancer risk, and mitigate metabolic syndrome.[2–6]
Fasting can also mitigate and even reverse autoimmune diseases, exert anti-inflammatory effects in the body, and prevent immunosenescence, or immune system deterioration.
In today’s post we will dig more into the immune benefits of fasting and look specifically at fasting’s potential to help those with multiple sclerosis and asthma.
Fasting, inflammation, and immune function
During the month of Ramadan, Muslims worldwide focus on prayer and abstain from food from dawn to sunset each day. The holiday thus offers researchers a prime opportunity to study the effects of intermittent fasting (IF), the practice of breaking up the day (or week) into periods of eating and non-eating.
To this end, a cross-sectional study by Faris et al. investigated the impact of Ramadan fasting on inflammatory cytokines and immune biomarkers. The researchers assessed 50 healthy volunteers one week before the start of Ramadan, after three weeks of fasting, and one month after the end of the holiday.
Relative to before or after Ramadan, many markers were significantly lower (better) in the participants during their month of fasting. Specifically, the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNFα) were all lower during the fasting month, as were both systolic and diastolic blood pressures, body weight, and body fat percentage. Although the counts of some immune cells were decreased during fasting (total leukocytes, monocytes, granulocytes, and lymphocytes, specifically), they still remained within normal, healthy reference ranges. In other words: Ramadan fasting decreased inflammation without significantly suppressing immunity.
Ramadan fasting decreased inflammation without significantly suppressing immunity.
Whereas Ramadan lasts only one month and entails a rather intense fasting regimen, moderate caloric restriction (CR) for longer periods of time has also been shown to support the immune system.
A multi-center, randomized clinical trial by Meydani et al. studied the effects of CR on 218 healthy, non-obese adults between 20 and 50 years of age. Seventy-five of the participants ate ad-libitum (AL, as much as they liked), while 143 were instructed to reduce their caloric intake by 25%. All of the patients were tested and assessed through various metrics at baseline, after 12 months of the eating plan, and again at 24 months.
hs-CRP and TNFα levels were also lower in the CR group – by a whopping 40% and 50%, respectively.
Unsurprisingly, relative to AL group, the CR participants were slimmer: they lost over 10% of their original body weight. Perhaps more interesting, however, were the findings related to inflammation and immune function. Those practicing CR were also found to have lower blood levels of several inflammatory markers, including white blood cell (WBC) count, pro-inflammatory cytokines, and adhesion molecules. Serum high sensitivity C-reactive protein (hs-CRP) and TNFα levels were also lower in the CR group – by a whopping 40% and 50%, respectively. These markers are associated with systemic inflammation and are implicated in several serious illnesses, such as rheumatoid arthritis, juvenile chronic arthritis, psoriatic arthritis, Crohn’s disease, and multiple sclerosis.
Calorie restriction does not compromise cell-mediated immunity.
In another aspect of this trial, the participants received vaccines and then had their blood samples collected. The participants in both groups had similar antibody responses to vaccination, suggesting that CR does not compromise cell-mediated immunity. CR was thus shown to reduce inflammation without suppressing this important aspect of a normal immune response.
Fasting and multiple sclerosis
In a 2008 mouse study by Piccio et al., CR was shown to inhibit experimental autoimmune encephalomyelitis (EAE), an inflammation of the brain and spinal cord induced in animals as a way of studying MS.
At the biochemical level, CR was correlated with increased levels of corticosterone, a natural “steroid shot,” and adiponectin, a protein hormone produced by fat cells that fights inflammation, prevents the clogging of arteries, and improves insulin sensitivity. CR was also associated with decreased concentrations of the pro-inflammatory cytokine IL‐6. These findings suggest that CR could be a potential therapy for relapsing-remitting MS in humans.
Calorie restriction could be a potential therapy for relapsing-remitting MS in humans.
Intrigued with these findings, Piccio joined another group of researchers (Cignarella et al.) to see if IF could have similar effects as CR in the treatment of MS. In this study, both mice and humans were observed.
In mice, IF was shown to ameliorate the severity and the progression of EAE. IF not only lowered anti-inflammatory cytokines, but also by improved the quality of the gut bacteria (microbiome). In fact, when the mice eating a regular diet received fecal microbiota transplants (FMT, or “poop transplants”) of stool collected from the IF mice, their severity of EAE and spinal degeneration improved. These findings suggest that the benefits of IF on MS are generated at least in part by positively enhancing the gut flora.
The researchers then applied their findings to humans, treating those currently having a relapse of their MS symptoms. The findings echoed those of the mouse study: IF shifted both blood cytokines and gut flora in a salubrious direction in humans, engendering immunomodulatory benefits.
Fasting and asthma
In a study of overweight adults with moderate asthma, participants were asked to eat their usual diets – but only every other day. On the intervening days, the participants did a partial fast, consuming less than 20% of their typical caloric intake. The nine (out of ten) subjects that stuck with the plan lost an average of 8% of their body weight over the eight-week study period.
Perhaps more importantly, their asthma-related symptoms, asthma control, and quality of life metrics all improved significantly, as did their peak expiratory flow, a measurement of how well air flows out of the lungs. These benefits were observed within just two weeks of starting the eating plan, and stayed with the participants through the remaining six weeks of the study.
Asthma-related symptoms, asthma control, and quality of life metrics all improved significantly.
While the eating plan did not seem to improve all parameters of lung function, it did improve cholesterol and triglyceride levels, and dramatically decreased various markers of oxidative stress and inflammation.
In another study of asthmatics, 29 participants with well-controlled asthma were observed during the month of Ramadan. While Ramadan fasting did not improve all aspects of spirometry, it was associated with improvements in peak expiratory flow and peak expiratory flow variability.
These findings suggest that CR on alternating days or fasting can be a beneficial strategy for people with asthma.
We may now add immune modulation to the ever-growing list of fasting’s health benefits, and multiple sclerosis and asthma may likewise be appended to the list of conditions potentially helped by abstaining from or limiting intake of food.
Those wanting to try calorie restriction and intermittent fasting are advised to do so under the guidance of a healthcare provider, to ensure that nutritional needs are met and that the regimen maximizes the benefits and minimize the risks.
ReferencesClick here to see References
- Britannica. Fasting [Internet]. Chicago (IL): Encyclopædia Britannica; 2015 [cited 2020 Jun 22]. Available from: https://www.britannica.com/topic/fasting.
- Patterson R, Sears D. Metabolic effects of intermittent fasting. Annu Rev Nutr. 2017;21(37):371-93.
- Mattson MP, et al. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017;39:46-58.
- Anton SD, et al. Flipping the metabolic switch: understanding and applying the health benefits of fasting. Obesity. 2018;26(2):254-68.
- Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19(2):181-92.
- Nencioni A, et al. Fasting and cancer: molecular mechanisms and clinical application. Nat Rev Cancer. 2018;18(11):707-19.
- Choi IY, et al. Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence. Mol Cell Endocrinol. 2017;455:4-12.
- Faris MAIE, et al. Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects. Nutr Res. 2012;32(12):947-55.
- Meydani SN, et al. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans. Aging (Albany NY). 2016;8(7):1416-31.
- Lin J, et al. TNFα blockade in human diseases: an overview of efficacy and safety. Clin Immunol. 2008;126(1):13-30.
- Piccio L, et al. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis. J Leukoc Biol. 2008;84(4):940-8.
- Tanaka T, et al. Il-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295.
- Cignarella F, et al. Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab. 2018;27(6):1222-35.
- Johnson JB, et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med. 2007;42(5):665-74.
- Norouzy A, et al. Effects of Ramadan fasting on spirometric values and clinical symptoms in asthmatic patients. J Nutr Heal. 2013;1(1):23-7.