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One form of fasting may be best to fight inflammation — study

A new study adds evidence to the idea that a break from eating helps fight the pathology du jour.

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Fasting, scientists believe, is a natural, relatively safe way to reduce inflammation in the body. At the same time, anecdotal reports abound that fasting helps tamp down this seemingly common health condition. But how, exactly, the eating regime does this, is still under investigation. Now, new, preliminary research presented at the American Heart Association’s Scientific Sessions in November helps color in some of the details about fasting’s anti-inflammatory properties, highlighting one kind of fasting regime as potentially more powerful than others.

The discovery — The research team found that people who followed a regime in which they fast for a 24 hour period at least once a week for 26 weeks had high levels of galectin-3 compared to a control group of people who did not fast. Galectin-3 is a kind of cellular-repair protein associated with easing inflammation.

The study involved 67 participants with metabolic issues linked to inflammation, including type-2 diabetes and conditions that put them at risk of diabetes. Thirty-six participants were charged with following a schedule in which they consumed only water over a 24-hour period — initially, they did the fast twice a week for four weeks, and latterly once a week for 22 weeks. The other 31 participants didn’t change their eating patterns.

Fasting on this schedule, the researchers conclude, may have some of the same effects as SGLT-2 inhibitors, a class of drugs used to lower blood sugar in people with type 2 diabetes.

“From what we see, fasting periods were used... as sort of a healing mechanism.”

Inflammation has a complex relationship with insulin resistance, the two instigating each other in a compounding cycle. This may explain why the researchers also found lower rates of biomarkers associated with resistance to insulin in the fasting group.

What’s new — The study is a part of the Intermountain Healthcare Heart Institute’s research program investigating low-frequency intermittent fasting and its potential health benefits beyond weight loss.

“We’re more interested in the protective effects for the heart and for the metabolism,” Benjamin Horne, director of cardiovascular and genetic epidemiology at the Intermountain Healthcare Heart Institute, tells Inverse.

“We expected that the benefits of fasting are primarily focused on improving risk related to diabetes and to heart disease,” he says.

Can intermittent fasting reduce inflammation?

Here’s the background — Inflammation is the immune system’s way of immediately healing injury or fighting off bacteria. Chronic inflammation, which continues in absence of any such situation, can create havoc in the body. It has also become a pathology du jour in recent years. Mounting evidence links chronic inflammation to Alzheimer’s, cancer, gout, arthritis, asthma, Parkinson’s, multiple sclerosis, depression, and diabetes.

It could be that low-grade, long-term chronic inflammation is increasingly common because our pollutant-rich, chemically-doused environment tricks the immune system into always sensing a bodily invader.

Several past studies have also shown reductions in various biomarkers related to inflammation in both people and lab mice who go without food for significant periods of time. The mechanisms are not well understood and the findings are limited to metabolic signs of inflammation or of control of inflammation, rather than long-term health benefits.

Muslims observing Ramadan volunteered for some of the first studies on fasting and inflammation.

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Horne says the effect may have its roots in our evolution. In times when food was scarce — times that might be mimicked by fasting — individual tissues and organs might enter “a self-protection mode” and limit potentially harmful reactions like inflammation.

Ancient humans “survived times of low, low food availability, they had mechanisms in their DNA that would help them survive,” he says.

Valter Longo, professor of Gerontology and Biological Sciences at the University of Southern California, tells Inverse fasting may act as a reset for the body, calling off the emergency inflammatory response.

“From what we see, fasting periods were used by all kinds of organisms, including humans, as sort of a healing mechanism,” Longo says. “So whenever someone had a major inflammatory problem, which could have been due to an infection or a wound, then fasting was a natural way to activate the body’s innate way to repair and replace.”

What is “low-frequency” intermittent fasting?

Fasting is just abstaining from eating — many people do so on occasion for religious reasons. Intermittent fasting means fasting for a period and then eating during another — one version of this is “low frequency” fasting, in which a person abstains from food for a day or a couple of days in a week, rather than for a certain number of hours every day.

Longo believes a longer fasting period at a time is probably necessary to see an anti-inflammatory benefit from the practice — that gels with the results of the regime tested in the new study.

“If you fast every day for 10, 12, 16 hours, you may or may not have any benefits of inflammation. There may be some but we are still in the early stages of understanding,” he says.

In this study, the fast period lasted at least 24 hours, bringing it in line with the longer period fast Longo thinks may be effective in reducing inflammation.

However, more research is needed before scientists can say such a regime is effective in reducing inflammation, and how it might stack up compared to other, more established treatments and lifestyle choices designed to tamp down chronic inflammation.

Introduction: Intermittent fasting decreases cardiometabolic risk factors, heart failure (HF) risk, and type 2 diabetes risk. Sodium-glucose transport 2 (SGLT-2) inhibitors reduce diabetes and HF risk and a study of canagliflozin reported that it raised galectin-3 levels (Januzzi 2017). Previously in the WONDERFUL trial (NCT02770313), intermittent fasting caused declines in the Metabolic Syndrome Score (MSS) and homeostatic model assessment of insulin resistance (HOMA-IR). This study evaluated intermittent fasting’s effects on galectin-3 in a post hoc analysis of the WONDERFUL Trial.
Methods: People aged 21-70 years were enrolled who had ≥1 metabolic syndrome feature or type 2 diabetes, were free of anti-diabetic and statin medications, and had elevated LDL-C. Subjects had 26-week galectin-3 data (N=67; n=36 intermittent fasting, n=31 controls). Subjects were randomized to a 24-hour water-only fasting intervention (fasting twice per week for 4 weeks, then once each week for 22 weeks) or a parallel control arm (ad libitum eating). This study evaluated the 26-week galectin-3 change score and other changes in HF biomarkers.
Results: At 26 weeks, the galectin-3 change score was increased in intermittent fasting (0.575±2.63 ng/mL) vs control (-0.624±2.79 ng/mL; p=0.021). Changes in galectin-3 were inversely correlated with HOMA-IR change score (r= -0.288, p=0.018) and MSS change score (r= -0.238, p=0.052). Changes in galectin-3 at 4 weeks (intermittent fasting: 0.345±2.68 ng/mL; control: -0.465±3.18 ng/mL; p=0.27) and 13 weeks (fasting: 0.917±4.96; control: -0.097±2.83 ng/mL; 0.15) were not significantly different. B-type natriuretic peptide went down in intermittent fasting (-0.328±12.29 pg/mL) but this was not significant compared to controls (15.50±75.34 pg/mL, p=0.23). Other HF biomarkers were unchanged.
Conclusions: Water-only 24-hour intermittent fasting increased galectin-3. This rise in galectin-3 was correlated with declining HOMA-IR and MSS and may be similar to reported effects of SGLT-2 inhibitors. Increased galectin-3 may be an adaptive response that could prevent chronic disease by decreasing inflammation, ameliorating insulin resistance, or modifying related mechanisms.

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