Fast Times at PPAR-y

February 10th, 2012  |  Published in Stumpblog, Why eat (or not)  |  7 Comments

Oh, please, please laugh at this title. Please! And enjoy the buffet.

The world’s truly oldest profession, fasting, is making the news lately. Exciting evidence suggests that periodic fasting carries a number of health benefits. (More on this in a future article, but for now, check out the free e-book Experiments with Intermittent Fasting from John Berardi, to which I humbly contributed my own perspective.)

Leaving aside the current state of the research, let’s accept for now the premise that fasting does, in fact, have significant health benefits.

The question is: Why?

We certainly don’t have all the answers just yet. But one clue may come from an intriguing place: the role of PPAR-ƴ (pronounced “pee-par-gamma”; yes, I know, just like my Ukrainian grandad used to joke, “It sounds just like it’s spelled”).

PPAR is an acronym for peroxisome proliferator-activated receptor. The ƴ, or “gamma”, is one of three known subtypes. PPARs are nuclear receptor proteins, which means basically that they’re proteins that are active within a cell, and their job is to regulate the expression of genes.

Side note: PPARs are one of the reasons that your genetic “blueprint” is not your destiny. Genes are not an unbreakable plan for an inevitable march towards doom or elite performance; they’re simply a set of instructions that may or may not get executed, depending on other factors. Same thing happens in a big company, right? Sure, your expense reports might be rock-solid, but Marge in accounting stands between you and getting that fast return. Don’t piss her off, or getting your expense reports through will be like trying to push Homer Simpson through a pneumatic tube.

These little PPAR folks are part of the army of proteinous squiggles that act sort of like gatekeepers and gofers between the fundamental building blocks of “you” and everything else. And just like Marge and your wages, PPARs can affect some of the major functions of your cells.

Bear with me for a second through this biochem, because I’m going to simplify (and potentially ridiculize) it even more in a second.

OK, so, we’ve got our PPAR-ƴ guys. They’re found in adipose tissue — aka fat. PPARs do a bunch of things, including regulating fatty acid storage and glucose metabolism. They can affect lipid uptake (how we use fat) and adipogenesis (the creation of new fat cells). And they’re also important in cellular differentiation (cells deciding to grow up, get a haircut and a job), general metabolism, and… now this is cool… tumourigenesis (aka the birth and growth of tumours).

We want PPAR-ƴs to be fired up. When PPAR-ƴs are going gangbusters, inflammation goes down. Tumour growth appears to go down. Our insulin and glucose is better regulated. (In fact, PPAR agonists — which help activate PPARs — are one class of new diabetes drugs.)

All good. Oh, and we make more fat cells.

Wait… what? How the hell is that good?

Well, my pretties, get ready for your head to expand. Think of fat like radioactive material. It’s really useful stuff. It gives us power and energy. It’s naturally occurring. But in the wrong hands (hello, Iran), nuclear material is dangerous. It can be chemically active in problematic ways. And you sure as hell don’t want it wandering around where it shouldn’t be.

Our relationship with fat is complicated, to say the least. Never mind the fashion magazines; we grapple with fat issues at the cellular level.

Metabolic health includes proper storage and transport of fat. Normally our bodies are perfectly capable of handling fat. They love it, they know what to do with it, and everything is great. When fat can’t or won’t be stored properly, that’s when we have problems. So what this means is that more efficient fat storage and transport means better health.

Um. Wow.

Now, I’m not saying go run off and start stockpiling and shipping fat. What I mean is that in a healthy body, our system knows what to do with fatty acids and triglycerides. It tidies them away, tucks them into little cubbyholes, and releases them promptly when required. (This would be like Marge when she’s in a pleasant mood and her bureaucratic spirit is harnessed for the side of good.)

And I’m saying that proper and prompt fat storage is important. Yes, that means sometimes growing new fat cells.

Because when you can’t store fat effectively (which is what insulin helps us do), the fat still has to go somewhere. Since you’re fairly well contained by your bag of skin, you can’t exactly start flinging fat like snotballs away from yourself (although you do poop out some fat-based stuff, which is one reason why dietary fibre is a good idea). The fat ends up cruising your circulation, looking for skinny nerds to beat up and things to inflame.

Here’s where periodic fasting comes in.

Recent evidence suggests that fasting may be beneficial in part because of its effects on fatty acid and glucose metabolism along with insulin and PPAR-ƴ  (which seems to increase with intermittent fasting). These effects include helping the body properly transport, store, and use bodyfat, which also means that glucose and insulin metabolism operates properly.

As the authors of a recent study conclude,

It can be further hypothesized that periodic FW [feed withdrawal, aka fasting] may produce comparable effects as severe calorie restriction or bariatric surgery, where fasting glucose levels declined significantly in type 2 diabetics prior to significant weight loss and eventually leading to reversal of type-2-diabetes. Similarly periodic FW for a determined time may delay development of type-2 diabetes especially if prudence in food consumption and energy utilization is exercised between FW. (Mir et al, 2012)

Thus, paradoxically, intermittent fasting may help us get healthier and leaner because it makes nutrient transport and storage more efficient and effective, which helps other things to do their jobs properly. If the fat can get to where it needs to go more easily, you might actually end up leaner and healthier in the long run.

Remember, we don’t know all the pieces yet — the study above used pigs as a human model, for instance. But this may be one of the things that make you go hmm.

What does this mean in the real world? Well, it means that missing a meal occasionally might not be such a bad thing.

And if you’re struggling with insulin resistance and poor glucose management, or even more advanced Type 2 diabetes, you probably don’t have to go on a horrible restrictive diet — you might see health benefits from fasting for 14-36 hours now and again. This can be as easy as waiting a few more hours to eat breakfast, or having an early dinner and then no “evening snack”.

Remember that what makes the magic about intermittent fasting is the “intermittent” part — we aren’t talking about chronic restriction here. Nor should this be overly complicated. Just eat… and then occasionally not-eat for a while… and then eat again.

Combine the occasional period of not-eating with a healthy diet that aims to reduce inflammation, and optimize your body’s natural healing processes, and you might just stave off a cripping disease or two. (What is this diet, you ask? Well, see here.)



Fasting weakens cancer in mice. ScienceDaily Feb 8, 2012.

Hegarty, Bronwyn, et al. Peroxisome Proliferator-Activated Receptor (PPAR) Activation Induces Tissue-Specific Effects on Fatty Acid Uptake and Metabolism in Vivo—A Study Using the Novel PPARα/γ Agonist Tesaglitazar. Endocrinology 145 no.7 (July 2004): 3158-3164 doi: 10.1210/en.2004-0260

Matsusue, Kimihiko. PPARΒ/δ potentiates PPARγ stimulated adipocyte differentiation. FASEB Journal 18 (Sept 2004).

Mir, Priya, et al. Periodic 48h feed withdrawal improves glucose tolerance in growing pigs by enhancing adipogenesis and lipogenesis
Nutrition & Metabolism 2012, 9:10 doi:10.1186/1743-7075-9-10

Moran M. The evolution of the nutritional management of diabetes. Proc Nutr Soc 2004, 63:615-20.


  1. Miss Brooklyn says:

    February 10th, 2012at 12:15 pm(#)

    I tried intermittent fasting after reading Primal Blueprint. I made the serendipitous discovery that it helps with my IBS when fiber and coffee fail. Yeah, it’s diarrhea, but when you haven’t pooped in a week, you take what you can get.

  2. Andrea says:

    February 10th, 2012at 3:47 pm(#)

    One of my biggest questions (still not fully addressed by either myself or other IF’ers, so it’s not you, per se…) is how much caloric disruption can be tolerated to maintain the fasted state?

    In a nutshell – gum. OK? milk in coffee. 1 tsp? A Viactiv chew (20kcal)? Hell, black coffee itself has 7 calories, in theory.

    And to bring JB’s experiments into the discussion, what about greens powder? I was surprised he used that at all….

    Would LOVE to hear your thoughts.

  3. Erica says:

    February 13th, 2012at 5:51 pm(#)

    Dovetailing off Andrea: same question, but for low doses of meds that don’t need to be taken with food.

  4. Mistress Krista says:

    February 14th, 2012at 6:26 am(#)

    @Andrea & Erica: I’m not sure there is a perfect answer to this question, because the body is a complex biological system. It’s not on-off with a clear delineation. Frinstance, some folks have suggested that a low-protein semi-fasted state has similar effects (for example, getting up in the AM and having a tablespoon or so of heavy cream or coconut milk in one’s coffee). Others have suggested that the taste/presence of glucose/sweetened things might also be a factor. Still others have noted that the benefits of fasting might accrue simply with a very low caloric intake rather than a total fast. In our book on IF, Dr. Berardi discusses his use of BCAAs (branched-chain amino acids) postworkout in a fasted state as a means of preventing muscle loss. I believe Martin Berkhan also recommends BCAAs before training fasted.

    The point is: We don’t know.

    All we know is this: The preponderance of the evidence shows us right now that having intermittent periods of no or almost-no food seems to have beneficial effects on human health.

    I would also argue that our bodies are not as picky as our frontal cortex thinky brains are, and can accommodate a wide range of possibilities. So, eat sometimes, don’t eat other times for a little while, and don’t worry about the details too much. :)

  5. Erica says:

    February 14th, 2012at 10:25 pm(#)

    Makes sense. Thanks for response!

  6. danni a says:

    February 23rd, 2012at 10:47 am(#)

    Thanks for this post. I have been practicing IF for about 2 months now, doing daily 14-16 hour fasts with a 8-10 hour feeding window. Once a week if I feel like it I’ll throw in a 24 hr fast.
    This in combination with a grain free diet has really helped my strength training beyond what I was doing before. What do I love about IF? actually experiencing REAL HUNGER. I think that feeling was lost to me before, and now that I let myself experience true hunger, food just tastes better. It is pretty sweet deal.

  7. Howtolosebellyfatforwomentips says:

    March 2nd, 2012at 4:54 pm(#)

    Good post, I tried IF fasting but I’ll be honest, I tried it because it was the new hot topic at the moment. I struggled with the amount of calories needed to be eaten at night…wasn’t for me. I think this post does a great job of showing the WHY to this eating plan though, thanks!

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