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Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

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February 10, 2015

What’s Messing with Your Appetite? Three Possibilities.

By Mark Sisson
62 Comments

HungryAlthough a few weeks ago I explained how “stop eating so much” is bad weight loss advice and how “calories in, calories out” tells us very little about the cause of obesity, the fact remains: for whatever reason (and there are many), people who gain weight have eaten more energy than they’ve expended. Something is causing them to eat more food than they need. Something is making the hungrier than they need to be, desirous of more food than they require for sustenance and weight maintenance. What could it be? There are the basic remedies. Eat more protein to promote satiety. Reduce carbs, increase fat. Get enough sleep and limit stress as best you can. These are proven ways to normalize your appetite, but you already know about them. I also have a few speculatory ideas that you may not have considered, and today I’m going to discuss them.

Before donning your skeptic hats and demanding randomized controlled trials, remember that these are theoretical appetite perturbers. Most of the ideas I propose draw on in vitro studies examining potential mechanisms, observational studies looking for hypotheses, circumstantial evidence, and the occasional controlled trial. These are not intended to be absolute statements of truth. These are conversation starters that get you thinking and experimenting. They may work. They may not work. They are, however, safe to explore on your own.

Grain protein fragments causing leptin resistance.

Leptin fills a great many roles in the body, but it’s probably most well-known for its inhibitory effect on appetite. Using the amount of body fat you’re carrying as a barometer, leptin determines how well-fed you are and adjusts appetite accordingly. In a perfect world, body fat secretes leptin and leptin receptors in the brain receive it. Appetite is regulated, weight is maintained. But what if something blocked that connection between leptin and its receptors? You could have sufficient circulating leptin but without the brain’s ability to perceive it, the appetite suppression would never occur.

The idea that grain proteins might bind to the leptin receptor and induce leptin resistance was first proposed by Staffan Lindeberg in his 2005 paper. In a recent paper, researchers put gluten through in vitro digestion (where they simulate human digestion using pepsin and trypsin), filtered it off using either a spin-filter (no heat) or 100°C (heat), placed the two different gluten digests (great magazine name right there) with leptin and leptin receptors in an environment simulating human serum, and observed the reactions. At a simulated serum level of 10 ng/mL, gluten that had undergone spin-filtration inhibited leptin binding to leptin receptors by 50%. Since breastfeeding mothers on unrestricted diets have shown mean serum gluten levels of 41 ng/mL in the past, this in vitro finding could have ramifications beyond the test tube.

Too many aceullular carbs.

A “cellular carb” is glucose that’s stored inside a fiber-bound organelle. Think tubers, roots, fruits, leaves, and any whole food source of carbohydrate. Even a whole wheat berry, for example, is an example of a cellular carb until you turn it into flour.

An “acellular carb” is dietary glucose that’s been liberated from its cellular cage. Think flours, especially cereal grain flours, and all the foods made using flour, like cookies, cakes, bread, pretzels. Think fruit juice. Think pulverized dried fruit bars and energy bars.

In his 2012 paper, Ian Spreadbury proposes that excessive intakes of these acellular carbohydrates are responsible for our dysregulated appetites and the modern obesity epidemic. When we eat cellular carbs, they remain intact and inaccessible until breached by digestive processes, reducing the concentration of carbohydrate available to the gut bacteria. When we eat acellular carbs, the glucose is immediately released into the digestive chyme, increasing the concentration of carbohydrate available to the gut bacteria far beyond evolutionary precedent. Spreadbury shows how this might perturb appetite:

  1. This concentrated influx of dense carbohydrate into the gut produces an inflammatory microbial population that increases production of bacterial endotoxin and increases intestinal permeability.
  2. Increased intestinal permeability allows bacterial endotoxin into the body.
  3. Once in circulation, bacterial endotoxin induces leptin resistance and (in rats) increases food intake.

We are not rats, nor have controlled human trials been done looking at the effect of chronic acellular carbohydrate intake on leptin resistance, appetite, and bodyweight. But we obtain the vast majority of our carbohydrates from acellular sources, and we’re the fattest we’ve ever been in human history. Meanwhile, for the vast majority of human history we obtained the vast majority of our carbohydrates from cellular sources and remained lean and fit. And studies of modern pre-industrial cultures like the Kitava who consume ample carbohydrates in the cellular form of tubers and fruit show little evidence of obesity, leptin resistance, or dysregulated appetite.

As a little thought experiment, ask yourself two questions. Which carbohydrate foods do the healthy, lean people you know prefer? Which carbohydrate foods do the overweight, unhealthy people you know prefer? Then, take a look at this chart showing the carbohydrate density of modern and ancestral carbohydrate sources. Notice anything?

It’s a plausible hypothesis — don’t you think?

PUFA-induced munchies.

Induction of the munchies can be a pleasant way to increase one’s enjoyability of food, but it’s a double-edged sword: the worst kind of food looks especially delicious when the right cannabinoid receptors are triggered. And due to the presence of endogenous cannabinoids, or endocannabinoids, we can get the munchies without even trying.

In animals (including humans), the endocannabinoid anandamide is an important hunger signal, increases appetite, and intensifies the reward we get from junk food. There’s extensive animal research showing that dietary linoleic acid, the PUFA found abundantly in the seed oils used in everything these days, contributes to a rise in anandamide. For instance, a 2012 paper showed that increasing the linoleic acid content of a mouse’s diet from 1% to 8% of energy (paralleling the rise of linoleic acid in the human diet over the past century) tripled anandamide levels and increased food intake, body weight, and body fat. Dropping the linoleic acid back down to 1% of energy resolved the issue; so did adding fish oil at 1% of energy.

These were mice, yes. Anandamide is active in humans, though, increasing appetite and the reward we get from food. And there’s some evidence that the same treatment in the linoleic acid-fed mice that normalized their anadamide and appetite levels — omega-3 supplementation — works in humans. A group of mildly obese German men were split into two groups. One group got 4 grams of powdered krill every day and the control group received nothing. The krill powder group reduced their serum anandamide levels by 84% after 24 weeks; this improvement was mediated by an improvement in EPA and DHA status. There’s no indication of the baseline diet, but since this indicates that German adults get about 6.5% of energy from PUFAs, it probably contained significant amounts of linoleic acid.

Although I find the evidence for excessive linoleic acid’s stimulatory effect on appetite to be compelling and worth a closer look, it remains to be seen if soybean oil can make you wonder what if, like, the universe is all just a simulation, dude? These ideas are easy enough to explore on your own.

  • Stop eating cereal grains, especially gluten-containing grains. Be strict for a month. How’s your hunger?
  • Stop eating processed food, flour-based food (even coconut or almond flour paleo baked goods), and other acellular carbohydrates. Be strict for a month. How’s your hunger?
  • Reduce linoleic acid intake to 1% of total energy. Be strict for a month. How’s your hunger? (Additional trial: increase long chain omega-3s from marine sources to 1% of energy.)

Not too complicated, completely safe (no doctor required), and likely to have an effect. Why not give it a shot?

Let me know how it goes for you. Thanks for reading, everyone.

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62 Comments on "What’s Messing with Your Appetite? Three Possibilities."

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Erica
1 year 7 months ago

I read this as I ate a bowl of cereal … and I know every time I start my day with cereal versus protein I don’t have as much energy for the day!

Zach
1 year 7 months ago

Lol then why do you do it?

Storm
1 year 7 months ago

The last bowl of cereal I ever had was 3 years ago, and haven’t looked back. If I feel like carbs, rice, meat and Veggies works well.

Nitin
1 year 7 months ago

I think you need to hear this. A bowl of cereals it the worst way to start your day. You get homogenized milk (denatured proteins and fats), sugar and grains, possibly gluten grains. Good news is it will only get better. If you aren’t ready to switch to pastured eggs, a small step up would be rolled oats in raw milk and just a bit of honey. Baby steps.

Groktimus Primal
1 year 7 months ago

This is the high quality MDA style post I know and love!

Larry
1 year 7 months ago
Love the insights. Having lived through constant hunger to never hungry I was thinking about this a lot. I have related ideas. Toxics in non-organic fruit and veggies, processed foods leads the body to intentionally store a lot of it as fat even beyond the normal fat storage of a high carb meal. What if the body is incredibly smart and ‘knows’ there are toxins in processed food, so routes as much as possible the food into fat storage. Even more than it would otherwise? So an organic potato without round up on it would lead to slightly less food… Read more »
Jason
Jason
1 year 7 months ago

Are green shakes still considered cellular? Those which have simply been blended (rather than “juiced”), of course.

Wildrose
Wildrose
1 year 7 months ago

That’s a good question and I’d like to know too. 🙂 I think they are, but I’m not sure.

Zach
1 year 7 months ago

Essentially, anything ground is Acellular, hence the recommendation to exclude coconut an almond flour. Your blender broke down te cell aleady so your body skips that energy intensive step.

Sofie
Sofie
1 year 7 months ago

Difference being that greens still don’t have a lot of carbs in them.

Jason
Jason
1 year 7 months ago

I, too, am very interested in this question. I have a Nutribullet where the claim is extraction versus blending… I like to have a few a week as it’s an easy way to get servings of kale, parsley, spinach, tomatoes, endive, watercress, chard, chia seed, maca powder, flax seed, spirulina, or whatever I have in my diet…

Anyone have further thoughts along the acellular fronts?

Erik
Erik
1 year 7 months ago

It’s just a blender that only has a puree speed. If you’re sticking to mostly low carb items, like non-starchy vegetables, then it probably makes little difference.

John Mondin
1 year 7 months ago

I stopped eating cereal grains and feel much much healthier. I think there are a lot of sugars in the grains that aren’t healthy for you as well. Thanks for the healthy start to my day tip!

Nitin
1 year 7 months ago

Couldn’t agree more. Only proteins and fats in the morning is the way to go for me and sometimes only fat breakfast works great too (bulletproof or any other fatty coffee).

Nocona
Nocona
1 year 7 months ago

Love the idea about stopping the nut flours for awhile (paleo banana bread anyone). I occasionally partake of those, but have always felt it was kinda like a cheat day.

Margarey
Margarey
1 year 7 months ago
I have been feeling INSATIABLE hunger the last few weeks. I have only been obtaining about a 70/30 due to corn tortilla and tortilla chips + a hamburger and a pizza night all in the same week (I normally have a hamburger once every 3 months and pizza even less! But I was CRAVING IT) 🙁 But I am still getting a ton of meat, veggies, and lots of good fats. My husband says he thinks I am pregos… but have never been, so I don’t know if that is something that would show through hunger so early on. I… Read more »
Josh Klemme
Josh Klemme
1 year 7 months ago

Time for a pregnancy test.

Becca
1 year 7 months ago

^^ Lol. But yes, I would agree 🙂

b2curious
b2curious
1 year 7 months ago
There are no hard and fast rules about pregnancy symptoms, but yes, hunger can increase very early on, and carb cravings are fairly normal. With my oldest, my initial symptoms were mild and PMS-like, without the irritability. I had a slightly increased appetite (this varies greatly among women) and breast tenderness, even before my period was due. (It should be noted that some women never miss a period while pregnant, though it is generally lighter.) The fact that you haven’t gained weight under a situation where you normally would, indicates that something has changed. However, it could be that your… Read more »
George
George
1 year 7 months ago
Anecdotally, I consider the idea about acellular carbs absolutely true. Both my wife and I have gone months where the only carbs we eat are fruits, veggies, and safe starches (white rice mostly). We lose weight easily, and have no cravings between meals. If anything, I have trouble keeping weight on during these times (I’m a fit and active ectomorph). When we add any sort of processed carbs or sugars, even though they are all made of gluten-free and “paleo” ingredients, we both notice an immediate increase in that “rumbly tummy” type of hunger. The more we feed this “carb… Read more »
Christine
Christine
1 year 7 months ago

Very cool article! I’ve noticed that my appetite is WAY more under control when I eat a protein and fat heavy whole foods diet (versus around the holidays when I indulge in more treats and my appetite goes out of whack!). But I never knew about the cellular / acellular carbs part. It makes a lot of sense to me and is definitely something I will keep in mind when choosing carbs in the future (even “paleo” friendly flours like almond & coconut). Thanks!

Jacob
1 year 7 months ago

Makes sense… I can go to a place that serves bread and eat WAY more than I normally would **cough cough** Red Lobster **cough**

Curtis
Curtis
1 year 7 months ago

Those cheddar biscuits are like crack.

Jacob
1 year 7 months ago

Haha I’m utterly convinced they do have some nefarious drug in their biscuits because it’s nearly impossible to stop after you’ve eaten one.

Marti
Marti
1 year 7 months ago

I find that if I pulverize them and inject them directly into my blood stream I can get by with only having one. Otherwise, all bets are off.

JM
JM
1 year 7 months ago

I’ve been reading your site for years, and one of the things I wish you would address are the roles of infection, micronutrient deficiencies, and finally lack of calories PERIOD in appetite dysregulation. Sometimes the answer isn’t less carbs, more protein, more fat, but a real true issue like a parasite, hypothyroidism (from either a nutrient deficiency or infection), or the person has an eating disorder and 1200-1500 calories a day isn’t really the appropriate amount of food for them to be eating for weight loss.

Jacob
1 year 7 months ago

I don’t think Mark has ever said not to count calories to maintain a healthy weight. He HAS said calories aren’t the end-all-be-all for weight loss. What you eat is as important as how much you eat.

JM
JM
1 year 5 months ago
not that any one will care at this point on this comment, but here goes: In this post where someone worries about not having appetite/getting in too few calories on Primal, MSisson says, “Hey, maybe that’s a good thing…listen to your body” http://www.marksdailyapple.com/eating-too-little-food-paleo-primal/#axzz3W4XKm3bG Then, in the same post, he says – BUT – watch out for these signs that also could be from your body that you’re not eating enough – feeling a little more cold, feeling a little more tired or apathetic, having a little bit more belly fat. To which my response is, thanks for these awesome markers… Read more »
Pete
Pete
1 year 7 months ago

Could the acellular carb thing be one of the reasons why rice-eating populations have been seen as healthier than grain-eating?

Pastor Dave
Pastor Dave
1 year 7 months ago

Those darn endocannabinoids!!! I have NO trouble avoiding acellular carbs–but if I delve into them on a cheat day I end up a glutton! And that’s more than weight gain–for me it’s a sin!

During the week my wife and I are opposite eaters– she can eat grains and stuff all day–not me.

If i could stay at church all day Sunday and avoid the home pantry and the kids coming over and munching for hours– I’d be at my ideal weight already!

Storm
1 year 7 months ago

..sounds like you need to give that home pantry a clean out. I find if its not in the house, then the cravings will pass by the time I decide I want to go to shop. Like shonky salespeople “Don’t let them in the front door to begin with” – lol

Pastor Dave
Pastor Dave
1 year 7 months ago

You’re correct–but I’d have to “clean out” my carb loving wife too!

Jack Lea Mason
Jack Lea Mason
1 year 7 months ago

+1

Julie
1 year 7 months ago

I am halfway through the whole30 and have not had gluten, coconut or almond flour or any grains for about two weeks now. My appetite has diminished so much that I was actually thinking this morning that now I could do one of those 24-hours fasts that you talk about on this site. Prior to this experience, I would have been too hungry to even attempt it!

Carly
Carly
1 year 7 months ago

Ok this article is great and would explain my weight staying where it is.. I’ve been strict paleo/primal for about 9months but do have baked paleo goods each week that I bake myself but always thought it would just count as my nut and banana intake for the day. But it makes them acellular carbs using almond and macadamia meal, bananas, berries and eggs..

Thanks, going to give 30days of no acellular carbs a go and see how it works out 🙂
Ps I love this site 🙂

Pastor Dave
Pastor Dave
1 year 7 months ago

Hey Carly– I had the same problem but recently went back to IF and cut out any acellular carbs–its starting to work–not fast but it’s working

Carly
Carly
1 year 7 months ago

Hi! Seems silly but do you mean intermittent fasting when you say IF?

I have officially cut out my acellular carbs and reduced my carb intake fullstop for a little while to go into a ketogenic state for a couple of weeks.. see how I go ????
Cheers

b2curious
b2curious
1 year 7 months ago
Yeah, it could explain things for me too. I’d always blamed the fact that I don’t get enough sleep during the week, which is definitely a factor. However, during the week, my breakfast is a smoothie made with coconut milk, half-thawed fruit and berries, vanilla, and honey. On weekends it’s bacon and scrambled omlets. (What most people would turn into an omlet, i just scramble with my eggs.) I do eat less on weekends, but is it because I’ve gotten more sleep, am eating protien first thing in the morning, the lack of acellular carbs, or some combination of the… Read more »
Debbie
Debbie
1 year 7 months ago
I believe that the most important influence on hunger, cravings and insulin resistance/metabolic disorder is added/free fructose. There are multiple recent studies showing that fructose which is not part of whole food overwhelms the liver, leading to insulin and leptin resistance. See nofructose.com and davidgillespie.org/12-ways-fructose-destroys-your-body/ Fructose is found in all sugar including honey, maple syrup, agave syrup, HFCS, coconut sugar, white and brown sugar, balsamic vinegar, dried fruit, fruit juice. Our liver can not cope with the influx, even if it is a natural source. Whole food has fibre and water which slow the influx of all nutrients. Sugar in… Read more »
Allison
Allison
1 year 7 months ago
I’d like to add another possible culprit- major disruption of gut bacteria. After a year of happily eating VLC I had to do a three week course of oral chemotherapy. There were not tons of side effects, except that all protein seemed disgusting almost immediately, and I started to crave carbs and sugar like crazy. I don’t know when or how I’ll get my gut and eating back to normal. Of course, most people don’t have to take toxic drugs, but what about a bout of stomach flu, or a course of antibiotics? I bet these could affect hunger via… Read more »
Juli
Juli
1 year 7 months ago

This is a really excellent question. So much interesting info about how our body’s flora influence us, in some cases quite profoundly. More importantly, I hope the chemo worked and you can address your gut health v. cancer. I’m sure you know there are tons of resources inc on MDA about rebuilding a healthy GI system. Best wishes for healing!

Kim
Kim
1 year 7 months ago
I recently had a medical issue where I was prescribed narcotic painkillers, which I feel totally wiped out my gut flora. I had the crazy carb and sugar cravings ALL THE TIME!! Prior to that time I did not have cravings. It took a couple of weeks after weaning myself off the narcotics that I was able to function normally again, i.e., not thinking about eating junk all the time. I also started to eat sauerkraut and take a strong probiotic/prebiotic. I feel much better, but I know I have a ways to go. Good luck on your journey to… Read more »
Erin
1 year 7 months ago

I’m curious for what condition you were prescribed oral chemo? I realize it is absolutely none of my business, but if you are willing to share, I’d be interested to know. I know methotrexate is sometimes prescribed for autoimmune disorders, which is scary!

Allison
Allison
1 year 7 months ago

Metastatic melanoma. The oral chemo is being treated as a stopgap – I’ve already gotten several of the brand new drugs that are truly miraculous. There are three new drugs on the market now that have good chances of causing full remission in people with melanoma, with almost no side effects to boot. Unfortunately, they don’t seem to have worked for me. Jumping to the next lily pad.

Kimberly
Kimberly
1 year 7 months ago

I’m still not clear on the difference between, for example, the juice of an orange vs. a pulverized orange (think Vitamix smoothies), vs. a whole orange, peeled and eaten as is. I always thought I was doing ok as long as I ate whole foods – I love a parsnip and cauliflower mash…

Lena
Lena
1 year 7 months ago

Where would mashed sweet potato and pumpkin fall? Are they as-cellular food?
I feel that whenever I eat either, my hunger increases. Is it better to bake whole, slice and chew?

Juli
Juli
1 year 7 months ago

I notice a difference when I eat mashed cauliflower v. roasted or raw. Maybe it’s a texture thing but I feel less full and notice that I’m less sated. Even with the added butter. I wonder if this is why. Since I rarely eat anything that isn’t a whole food (and I’m rarely hungry), this makes sense to me. Interesting.

healthywings
healthywings
1 year 7 months ago

We are not rats,
We are not rats,
We are not rats,
ok = got it….

Pastor Dave
Pastor Dave
1 year 7 months ago

But– if you are what you eat and you eat RATS….!

healthywings
healthywings
1 year 7 months ago

okay – I get your point (and ha!) but we are only what we absorb from what what we eat… 😉 (wink)

Sally Oh
1 year 7 months ago
I’ve been on a 2 month trial of 5 cups of carrot juice a day (since cut short). It’s a cancer cure. I want to write about it so wanted to give it a go. My lbs rumblings went crazy, of course. I knew it was the carrots but didn’t know about the acellular thing… kind of a double whammy: all that unchained fructose 🙂 When I first started this, I ended up drinking most of my juice at night because it was hard to remember during the day. I woke up a couple of mornings with a full-blown hangover… Read more »
Carly
Carly
1 year 7 months ago

Gosh it’s well known that cancer simply loves sugar, especially fructose so I’m wondering how that can be a cancer cure.

Sally Oh
1 year 7 months ago

Read Curing Cancer with Carrots. Excellent book, very detailed, quick read. She addresses the sugar issue, it’s not as simple as “cancer loves sugar.” Carrot juice alone has worked for many people, as has the Gerson Therapy. There are so many cures for cancer available to us.

LeslieB
LeslieB
1 year 7 months ago

Have you ever tested your fasting blood sugar the next day? I have and found that morning headaches were high-blood-sugar related, caused by too many simple carbs before bedtime.

Sally Oh
1 year 7 months ago

Yes, I agree. My ‘lbs’ abbreviation in my original post is low blood sugar.

Hemming
Hemming
1 year 7 months ago

I have the opposite problem. My appetite is low (I eat low carb) and I struggle to eat enough to have energy for working out etc.

Nitin
1 year 7 months ago

I am kind of the same boat and I am trying to put on lean mass. You may find eating a bit of carbs in the night helpful – like sweet potato or rice. To make them lower GI, boil and cool them and eat them the next day. I like to use carbs as a smart fuel.
It’s all proteins and fats till evening, then may be a piece of fruit and some whole food starches in the dinner with heaps of protein and fats and veggies.

Harper Henderson
1 year 7 months ago

The radio rage player post is definately the best i have read today.

Peter
Peter
1 year 7 months ago

Good thing acellular protein isn’t an issue or you’d be whey out of business in no time. 😉

Kit
Kit
1 year 7 months ago

Mark does like a joke after all.

prachi
prachi
1 year 7 months ago
hi !!! i am 29 years old woman from india . my weight is 83 and my height is 5ft 1 inch ….. so much fat i have 🙁 .. i want to reduce weight but i feel tis like impossoble to me in this life ….. i was 68 kgs in 2011 before my child birth . after his i continoulsy gain weight due to my overeating and non exercise routinr … now i want second baby in coming years and i know its really risky to get pregnant with this huge weight ..it will create so much disease… Read more »
James IV
James IV
8 months 10 days ago
I have been looking into this for a while, and I definitely believe there is something to the acellular vs cellular gut microbe train of thinking. What I’m a tad confused about is why cellular grains like whole oats, corn, and I believe even brown rice would still be recommended against? And white rice, which would be acellular is still okay? Also, where do beans and legumes fall into this. From thier structure I believe they are also cellular carbohydrates, and would be considered healthy? i certainly home it’s not still the Phytate and lechtin argument, since that seems a… Read more »
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