Can cold showers, winter plunges, and brisk walks in the chilly outdoors provide some of the same benefits as intense exercise—including weight loss and increased energy levels? Such a link has been suspected, because cold exposure is known to convert metabolically docile white adipose tissue (WAT) into metabolically active brown adipose tissue (BAT). This “brown fat” helps you stay warmer and burn more energy. But now there is some evidence that cold exposure doesn’t merely help you turn up your inner furnace, and burn off a little fat in the short term. It may actually lower your body’s weight set point by activating a hormone that is also released during intense exercise.

That hormone is irisin (pronounced “EYE-rissin”), a cytokine produced in skeletal muscle. From the initial evidence, irisin and its partner hormone FGF21 may provide lasting benefits by boosting your metabolism and inducing you to shed excess pounds.

Brown fat. BAT, or brown fat, is a very different kind of fat than WAT, or white fat. The mitochondria in BAT cells can quickly turn calories into heat. They do that by using the protein thermogenin (also called uncoupling protein 1 or UCP1) to bypass the normal efficient conversion of glucose or fatty acids into ATP, our energy storage medium, via oxidative phosphorylation. Instead, thermogenin “wastefully” oxidizes fatty acids to generate more heat, with minimal conversion to ATP. It’s like using gas to power a cheap camp stove instead of a highly fuel efficient automobile. While this seems quite “wasteful” if you are trying to conserve energy in times of food scarcity, it’s actually quite effective if your goal is generating heat to stay warm, trying to shed extra pounds, or trying to avoid accumulating them in the first place. BAT is activated after cold exposure, and is beneficial for weight management because it can increase resting metabolic rate by up to 20%. As if that weren’t praise enough, brown fat it has been reported to have several additional health benefits, including reduced triglyceride levels, reduced incidence of fatty liver, and increased bone mineral density.

Muscle contraction, shivering and exercise. Gretchen Reynolds, in a recent New York Times article, “Shivering as a form of exercise“, highlighted a just-published study in Cell Metabolism by Paul Lee and coworkers at NIH, demonstrating that vigorous exercise and exposure to the cold each activate production of a singular hormone — irisin — by a common mechanism. Discovered only in 2012, irisin is a special type of hormone known as a cytokine, and because it is produced by muscle it is classified as a myokine. As Lee et al explain,

Irisin is an exercise-induced myokine that is secreted into the circulation following proteolytic cleavage from its cellular form, fibronectin-type II domain-containing 5 (FNDC5). It reverses diet-induced obesity and diabetes by stimulating thermogenesis in rodents through increasing brown adipocyte-like cell abundance within white fat.

In the NIH study, experimental subjects who cycled at 65 degrees F until exhaustion saw their blood levels of irisin surge higher. Remarkably, subjects who rested at 50 degrees F for 30 minutes had irisin levels equally high as the exercisers — but with no physical activity other than shivering! And the amount of irisin secreted was proportional to the amount of exercise or shivering. The researchers concluded that muscle contraction is the common mechanism causing release of irisin in exercise and shivering. They hypothesize that shivering — the rapid contraction of muscle — evolved as an early means of generating warmth, so that irisin secretion is as an inherent product of muscle contraction, whether from cold exposure or from exercise.

Cold adaptation. Through irisin, shivering induces a basic type of cold-induced thermogenesis, called shivering thermogenesis or ST. The researchers found that ST is necessary to make muscles secrete irisin, causing the formation of brown fat. However, as brown fat accumulates, a second type of cold-induced thermogenesis kicks in, called non-shivering thermogenesis or NST. And non-shivering thermogenesis activates another hormone called fibroblast growth factor 21 or FGF21. (A boring and much less evocative name than irisin!). Because FGF21 is produced in brown fat, it is known as an adipokine. The more brown fat accumulates, the more non-shivering thermogenesis becomes the dominant response to cold exposure.

So basically, this is the way you adapt to the cold: at first you need to get cold enough to shiver so that your muscles produce irisin, which increases brown fat. And as brown fat accumulates, you no longer need to shiver as much because mere cold exposure produces FGF21, which reinforces brown fat accumulation. The good news is that once you are adapted, you no longer have to shiver to get the benefits of cold exposure, because FGF21 acts to sustain brown fat accumulation and its metabolic benefits. This is consistent with what I myself experience since I started taking cold showers years ago. The cold water induces a delightful warming effect–without shivering, unless the water is particularly frigid.

The systemic effect of cold exposure, leading to hormone-regulated adaptations, is classic example of hormesis!

Other routes to cold adaptation? If the researchers are right, high intensity exercise, or anything that induces strong muscle contractions, should provide an alternative way to build up brown fat and become more cold adapted. That might include activities such as yoga or isometric exercises involving static tensing and relaxing of muscles. I don’t know whether this is true or not, but the theory would seem to predict it. So I’d be interested in any research or anecdotal experience that either supports or goes against this prediction.

Can irisin and FGF21 change your set point? Could ingestion or direct administration of irisin provide an effective weight loss remedy? in 2012, Bruce Spiegelman and others at the Dana-Farber insitute reported that direct injection of irisin into mice increased BAT levels and induced weight loss. After 10 days of administration to obese “diabetic” mice, blood sugar and insulin levels were normalized, and no adverse effects were observed. Furthermore, the human and mouse forms of irisin are identical. Whether or not this could lead to effective weight loss therapy, the experimental observations provide additional support for the role that irisin plays in regulating energy metabolism.

Weight loss and improved metabolism though increased BAT-induced thermogenesis sounds great. But wouldn’t our brain and metabolism try to resist such changes by homeostatically defending a “set point” weight? How do we know that homeostatic processes won’t compensate for the increased rate of thermogenesis by increasing appetite and by reducing the desire to exercise or otherwise slowing down the metabolism. We are all too familiar with dietary and exercise interventions that work in the short term, but fizzle or even backfire in the long term.

Body weight — actually body fat mass — is controlled centrally by the hypothalamus, the brain’s thermostat. The hypothalamus controls energy balance and fat mass by sensing and integrating incoming signals from energy molecules (glucose, fatty acids, ketones), hormones (leptin, insulin) and gut peptides (ghrelin, CKK, etc). Some have argued that each of us has a fixed “set point” weight, a natural weight that our body defends. It is argued that we can deviate from our set point weight in the short term, but we will eventually and inevitably return to that set point . Others have gone further to point out that attempts to evade this reality by crash diet and exercise programs often backfire, resulting in an actual increase of the set point. Seems like you can’t win for trying.

However, as I’ve argued in previous posts here and here, you can successfully lower your hypothalamic body fat set point. The key is to understand how certain dietary substances block access to the hypothalamus or inflame key receptors located there and, conversely, how intermittent intense exercise and other practices can enhance hypothalmic sensitivity, driving weight loss and improved energy levels.

I’ve long suspected that cold exposure could be one of those triggers that helps normalize hypothalmic sensitivity, but I didn’t have any direct evidence. And now it appears that irisin and its partner FGF21 may be mediators of this process.

A 2013 article by Piya et al in Endocrine Abstracts, describes evidence for Irisin as a central regulator in energy homeostasis. The authors identified irisin in human cerebrospinal fluid (CSF) and found that brain levels of irisin were significantly lower in obese pregnant women than in their lean counterparts. In addition, the authors found irisin is present in the paraventricular nucleous of the hypothalamus — present at the same locations as neuropeptide Y (NPY) a neurotransmitter that binds receptor neurons in the arcuate nucleous of the hypothalamus, increasing appetite and slowing energy metabolism. The suggestion here is that irisin could be acting to inhibit NPY receptors, thereby reducing appetite and increasing metabolism, Similarly, Sarruf et al. demonstrated that FGF21 acts on the hypothalamus to regulate energy, appetite and body composition. Their 2010 study, published in the journal Diabetes, showed that administration of FGF21 directly into the brains of rats significantly increased metabolic rate and insulin sensitivity, and reduced body fat.

The net effect, if the evidence holds up, is that elevated levels of irisin and FGF21 in the brain turn down the body mass “set point”.

Caveats. While what we’ve learned about irisin is promising, it should be noted that this is cutting edge science. It’s early days, and the precise role that irisin plays is not fully understood. It could be a major player or — as Peter Attia (whom I respect) suggests — a relatively minor one. We’ve seen hopes raised and dashed before for “obesity hormones” before. Injectable leptin was once proposed a panacea for obesity, until the early trials disappointed. The roles played by leptin resistance and regulation are now better understood. Similarly, we don’t know much about irisin receptors and sensitivity or resistance to the hormone. And even if irisin does regulate energy metabolism, it is not the only actor. Both central and peripheral regulation of weight and energy respond to multiple, often competing, sensory inputs. Eating a highly insulinogenic or inflammatory diet, or leading a sedentary lifestyle will counteract the beneficial effects of a single effector like irisin. So cold showers and brisk walks won’t do you much good if you eat poorly and don’t get off your duff. On the other hand, you might find — as I have — that cold showers help start your day by boosting your energy and tamping down your appetite.

Caveats aside, the discovery of irisin and its role in energy metabolism is a lead worthy of fuller investigation — both for its theoretical and practical value.

So try a cold shower! Or at least take advantage of the wintry weather, and energize yourself with a brisk stroll outdoors.

P.S. I would like to thank my brother Bruce for bringing the Reynolds article to my attention.

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