For today’s Dear Mark, I’m answering just one question from a reader. What are we to make of the new study purporting to show that saturated fat is the most harmful substance a liver can encounter? Should we remove all traces of it from our diets? Should we eat pure sugar? Quaff soybean oil? How relevant is an overfeeding study to a community of people dedicated to eating a sustainable, weight-reducing or -maintaining diet that includes saturated fat?

Let’s find out:

Hi Mark,

Did you see this study? http://care.diabetesjournals.org/content/early/2018/05/24/dc18-0071

What’s your take on it? Just got one of those classic emails from my vegetarian friend with only a link to the study and a smug emoji.

Oh yes, I knew this would come up after I linked to in on Weekend Link Love.

The title is “Saturated Fat is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars.”

I have a human liver. Do you? Probably. This is highly relevant to all of us, right?

Well, the first thing to understand is that this was an overfeeding study. Participants didn’t just eat a eucaloric diet with different energy sources. They each got a daily 1000 calorie snack on top of their normal diet for three weeks.

The SFA group ate 1000 extra calories in the form of butter, coconut oil, and blue cheese. The SFA:MUFA:PUFA ratio was 76%:21%:3%. Their liver fat increased by 55%.

The UFA group ate 1000 extra calories in the form of pecans, olive oil, pesto, and butter. Their SFA:MUFA:PUFA ratio was 21%:57%:22%. Their liver fat increased by 15%.

The Sugar group ate 1000 extra calories in the form of orange juice, soda, and candy. Their snack had no fat, all sugar. Their liver fat increased by 35%.

Saturated fat also increased lipolysis—the breakdown of fatty acids for energy—while unsaturated fat decreased it. Lipolysis normally increases during fasting or exercise. In that context, it’s a good thing and you end up losing body fat. If you have a steady stream of extra fat calories coming in, you won’t lose body fat. The researchers could have seized on this point and screamed “unsaturated fat inhibits lipolysis!” but they didn’t. Wonder why.

Also notable is the observation that overeating sugar increased de novo lipogenesis (creation of fat from sugar) in the liver by 98%. I was told that didn’t happen in humans, that de novo lipogenesis was a myth. Guess it can happen.

But, again, the most important thing to realize is that this was an overfeeding study. It wasn’t a weight loss study. It wasn’t designed to see which kind of diet spontaneously results in the most weight loss. It was designed to get people to eat 1000 extra calories from different nutrient sources to see how they affect liver fat. And they didn’t construct the entire diets around the hypothesis. From what I can tell, the participants ate their normal diets. Only the 1000 calorie overfeeding snacks were provided by the researchers.

You also have to consider choline. The more fat you eat, the more choline your liver needs to process that fat. In rats with fatty liver, supplementing with extra choline directly reduces liver fat. In Chinese women, a high choline intake protects against fatty liver. If the subjects didn’t increase choline as they increased fat overfeeding, they were bound to gain more liver fat. Remember: this was the whole point of the study.

Now with that out of the way, who is this study relevant for?

Those people who think keto gives them free license to consume as many calories as they can cram into their mouths. Don’t do that. Especially don’t do that with isolated sources of fat, including saturated fat. Overfeeding anything is bad news, unless you’re trying to gain lean mass, lifting hard and heavy on a regular basis, and the thing you’re overfeeding is whole food rather than isolated fat.

That’s it for today, folks. What are your thoughts? Does this study tell you anything new, or is it old news?

Let me know what you think down below. Take care, be well, and have a great day.

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The post Dear Mark: Saturated Fat More Harmful to Liver Than Sugar? appeared first on Mark’s Daily Apple.

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Insulin Dictionary Definition closeup highlighted in pinkInsulin does a lot of important things for us. It pulls glucose from the blood and fritters it away into our cells to be burned for energy or stored as glycogen. It prevents hyperglycemic toxicity to neurons, pancreatic cells, the arterial walls and the generation of excessive levels of reactive oxygen species. It even promotes muscle protein synthesis and helps augment muscular hypertrophy, especially following resistance training. Clearly, we need insulin. Without it, we’d die, as type 1 diabetics readily do without an exogenous source.

But this process goes off the rails when our cells become resistant to the effect of insulin over time. We secrete too much. Our levels remain elevated. It becomes harder to burn body fat. In fact, we end up in even more efficient fat storage mode.

I’ve shared about nutritional means to enhance insulin sensitivity in the past. What about other non-dietary strategies?

Lose Weight

Since insulin resistance is often the body’s response to energy excess (too much energy in), losing weight (increasing energy out) improves insulin sensitivity. Losing abdominal fat is particularly effective for increasing insulin sensitivity.

Lift Weights

Lifting heavy things, particularly with great intensity, improves insulin sensitivity by an interesting mechanism: non-insulin dependent glucose uptake happens immediately after the workout, which allows your muscles to replenish glycogen without insulin. According to some researchers, “the effect of exercise is similar to the action of insulin on glucose uptake.” I’d say not having to secrete any insulin makes you effectively insulin-sensitive.

Practice Sprint Intervals

An overloaded, energy-replete cell is an insulin resistant cell. An empty, “starving” cell is an insulin sensitive cell. Any exercise that burns glycogen and leaves your muscles empty and gaping for more will necessarily increase insulin sensitivity.

I can’t think of a faster way to burn through your glycogen than with a high intensity interval training session. Hill sprints or rower sprints are sufficiently intense and comprehensive.

Do Full Body, High Volume, High Intensity Training

Glycogen depletion occurs locally: high rep leg presses will deplete leg muscle glycogen, but they won’t touch glycogen in your arms, chest, and back. To fully deplete all the glycogen, you need to do full-body movements.

CrossFit WODs and other similar metcon workouts that have you doing pullups, squats, sprints, pushups, box jumps, and other compound movements—at high volume, in the same workout, and with minimal rest—will drain your glycogen stores and reduce the amount of insulin you need to replenish them.

Trigger Your Relaxation Response

Maybe it’s the quieting of the sympathetic nervous system, the “flight or flight” stress pathway. Maybe brief glimpses of bodhi reduce the amount of insulin required to dispose of glucose. Whatever’s going on, meditation (and likely other relaxation response inducing activities) improves insulin sensitivity.

Trigger Some Oxytocin

So, researchers might have used intranasal oxytocin for their purposes. But oxytocin is what we secrete in response to positive social interactions like sex, good conversation, dinner parties, breastfeeding, cuddling, and petting animals.

Ensure Adequate, Quality Sleep

If you’re coming from a place of already-adequate sleep, getting better sleep isn’t necessarily going to help your insulin sensitivity (although it might confer other benefits). It’s the absence of adequate sleep that destroys insulin sensitivity. By sleeping well, you’re restoring what was lost.

Train At Altitude

One study found that altitude hiking at 4500 meters improved glucose tolerance and insulin sensitivity. This isn’t feasible for everyone (4500 meters is really quite high, and not everyone lives near a suitable mountain). And, in truth, some people just aren’t ready to climb a mountain and hike around (in the study, some participants with low DHEA-S levels didn’t get the benefits), but it’s one way to improve it. Find the closest challenge you can in your region of the country.

Train In a Fasted State

While training of any kind promotes better insulin sensitivity, training in the fasted state enhances this effect. One study found that relatively high-intensity “cardio” performed while fasted increased subjects’ insulin sensitivity beyond the group who did the same training after a carb meal, even in the context of a normally obesogenic high-fat, high-carb diet.

Just Take a Walk

As the Primal Blueprint fitness concept of slow movement suggests, a simple walk can be quite powerful, particularly if you string them together to form a daily walking habit. A walk is good for glucose control after meals, but regular walking can have impressive effects on insulin sensitivity.

Never Stop Exercising

In other words, stay active for life. In a recent paper, both sprinters (aged 20-90 years) and endurance athletes (20-80 years) had far better insulin sensitivity than sedentary controls. Absorb this point: insulin sensitivity didn’t decrease with age in the two active groups. Even the 90-year-old sprinter retained good insulin sensitivity. The sedentary controls? Not so much. That says it all, I think.

Thanks for stopping by today, everyone. Let me know your thoughts, additions and questions below.

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The post 11 (Non-Dietary) Actions That Enhance Insulin Sensitivity appeared first on Mark’s Daily Apple.

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Hungry woman on a diet waiting with an empty place, isolated in whiteThis is an updated version of a Dear Mark column from 2012. You can find the original version archived here. The below has been completely updated for 2018.

The blank slate hypothesis has fallen. Everyone comes into this world imbued with attributes, characteristics, and predilections that are uniquely theirs. We’re all humans, but we’re a diverse bunch, and that makes it interesting. And though it also makes giving cookie cutter health advice impossible, I just take that as an opportunity to stand out from the crowd and provide actionable advice that genuinely helps real people.

A perfect example is biological sex. Anyone who’s lived with the opposite sex, been married, or had kids of different sexes knows that males and females are different—on average.

There’s a ton of overlap, don’t get me wrong.

We all need fat, protein, and carbohydrates. We all have the same requirements for sustenance and wellness. We all breathe oxygen, get stronger and fitter when we work out, use the same neurotransmitters, and produce the same hormones. The biological basics are identical.

It’s the details that differ. And matter.

Take fasting.

Fasting As Hormetic Stressor and the Influence of Biological Sex

Men and women both need to enter a “fasted” state in order to burn body fat. This should go without saying, but regularly undergoing periods where you’re not inserting calories into your mouth is an absolute requirement for weight loss and basic health, no matter your sex.

These periods are called “fasted states,” and they begin as soon as you stop processing the energy from your meal. An “intermittent” fast is an extended period of not eating done for the express purpose of weight loss and other health benefits. 

By definition, a fast is a hormetic stressor—a stressful input (no food) that in the right dose triggers an adaptive response that makes us stronger and healthier. Fasting triggers Nrf2, the “hormetic pathway” also triggered by other hormetic stressors like exercise, polyphenols, and radiation. Nrf2 initiates a series of defensive and adaptive mechanisms that help you respond to the stress and buttress your body against future stressors. But with too large a dose, a hormetic stressor can become a plain old stressor—one that overwhelms our defenses and harms us.

Making matters more complicated, the size of a hormetic dose is relative. What’s hormetic for me might be stressful for you. Many different variables affect how much of a hormetic stressor a person can tolerate.

With fasting, perhaps the most important variable to consider is your biological sex.

This really does make intuitive sense.

Biology cares most about your fertility. Can you reproduce? Can you produce healthy offspring that survive to do the same? These things come first.

And from that perspective, a woman’s situation is more precarious than a man’s.

You have a finite number of eggs, or “chances.” Men have an almost infinite supply of sperm.

When you are preparing to get pregnant, your body needs extra nutrients to build up a reserve and “prime the pump.”

When you are pregnant, the growing baby needs a reliable and constant stream of nutrients for almost a year. After a man gets someone pregnant, his biological involvement with the growing baby is done. What or when he eats has no impact on the survival of the growing baby.

After you’ve given birth, the growing newborn needs breastmilk. To make that milk requires additional calories and extra doses of specific nutrients. Modern technology allows us to skip nursing and go straight to the bottle, but your body doesn’t “know” that.

It all points to women being more finely attuned to caloric deficits. For example, women’s levels of ghrelin, the hunger hormone, are quicker to rise after meals.

This isn’t just relevant for parents or parents-to-be. Even if you’re not interesting in getting pregnant and having kids, or you have children and aren’t planning on any more, the ability to do so is strongly connected to your health. Reproductive health is health. As far as your body’s concerned, having kids is the primary goal and you need to be ready to do it as long as you’re able.

Where does fasting come in?

Fasting is simulated starvation. Amidst the most critical junctures of the reproductive process, even a single skipped meal can register as trouble. The problem with intermittent fasting is that it’s not just a one time thing. It’s a regular occurrence. Depending on the schedule you follow, you might fast every day, every other day, or once or twice a week. To the mostly unconscious body whose primary concern is your fertility, that can be alarming.

What does this mean for women interested in intermittent fasting Unfortunately, there aren’t many studies examining this question in women. There are a few, and I’ll get to those. First, let’s move to animal research.

What Animal Studies Tell Us

In male rats:

No matter the duration or degree of nutritional stress, a male rat’s brain chemistry responds with similar changes. Nocturnal activity and cognition stay fairly stable, regardless of the intensity of the fast. If you push the fast long enough, males will get a little wonky and frantic, but overall they maintain pretty well. It’s like they’re equipped with the ability to handle nutritional stressors.

In female rats:

Any degree of nutritional stress (fasting or mere caloric restriction) causes increased wakefulness (during the day, when they normally sleep), better cognition (for finding food), hyper alertness, and more energy. In short, female rats become better at finding and acquiring food when they fast, as if their bodies aren’t as well-equipped to deal with the stress of going without food. They also become less fertile, while the males actually become hornier and more fertile (probably to account for the females’ plummeting fertility). Ovary size drops (bad for fertility), adrenal gland size increases (which in rats indicates exposure to chronic stress), and menstrual cycles begin to dysregulate in proportion to the degree of caloric restriction.

One recent study found that placing young rats of both sexes on an intermittent fasting schedule had negative effects on fertility. While the male rats had lower testosterone, the female rats stopped ovulating, had trouble sleeping, and experienced ovary shrinkage.

What Human Studies Tell Us

One study found that while IF improved insulin sensitivity in male subjects, female subjects saw no such improvement. In fact, the glucose tolerance of fasting women actually worsened. Another study examined the effect of alternate day fasting on blood lipids. Women’s HDL improved and their triglycerides remained stable; men’s HDL remained stable and their triglycerides decreased.

Later, both obese men and women dropped body fat, body weight, blood pressure, total cholesterol, LDL cholesterol, and triglyercides on a fasting regimen. These people were obese, however, and perimenopausal women were excluded from the study, so the results may not apply to leaner people or women in the perimenopausal window.

One study compared continual calorie restriction (lower calories a little bit every day) to intermittent calorie restriction (lower calories a lot every once in awhile, similar to fasting) in overweight and obese women. Both groups lost a similar amount of weight, but the intermittent restriction group lost significantly more lean body mass. As I’ve always said, the kind of weight loss we want isn’t “weight loss.” It’s fat loss and lean mass retention (or gain). 

In the only heretofore extant human study on fasting and chemotherapy, seven females (including a 44-year old woman who was likely premenopausal, given when menopause usually onsets, though it wasn’t explicitly stated) and three males found that IF improved their tolerance to and recovery from chemotherapy.

Takeaway: male and female (mostly middle-aged, though that’s the population that generally gets cancer and undergoes chemotherapy) chemotherapy patients appear to benefit equally from IF.

What About the Effects of Training While Fasted?

One study looked at healthy men and women doing moderate intensity morning cycling either fasted (overnight) or fed (ate breakfast). Although both men and women displayed greater increases in VO2 max and resting muscle glycogen concentration in response to fasted cycling training, only men showed greater skeletal muscle adaptations when fasted. Women had better muscle adaptations when fed.

Another study placed both fasting and fed overweight women on an interval training protocol for six weeks. Both groups improved body composition and oxidative capacity to an equal degree. Being fasted or fed had no effect.

It’s sad to say, but that’s about it for fasted training studies in women. The vast majority deal with men.

How About the Psychological Effects Of Fasting?

In women, a two day fast shifted nervous system activity toward sympathetic dominance. Even though their cognitive function was unaffected, they were stressed out. In men, a two day fast shifted nervous system in the other direction, toward parasympathetic dominance. They were well-rested and relaxed. Their blood pressure dropped. Their cognitive performance improved.

How About Autophagy?

One of the main benefits of intermittent fasting is an increase in autophagy, the process by which our body clears out cellular debris and repairs damaged cellular structures like mitochondria. A decrease in autophagy is usually linked to increased aging; an increase in autophagy tends to stave off the ravages of aging. Fasting-induced autophagy is usually a good thing.

One of the most commonly-cited papers in  the intermittent fasting literature is this one, which shows how short term fasting induces “profound” neuronal autophagy. Only that might not be true for both sexes; another study shows how while “male neurons” respond to starvation as we’d expect—by undergoing autophagy—”female neurons” respond by resisting autophagy.

Less autophagy isn’t necessarily a bad thing. Certain diseases take advantage of the autophagy process, turning it against us by clearing out and killing healthy cells, and women tend to be less vulnerable to these diseases. But if you’re a woman aiming for autophagy, fasting may not be as reliable an induction method.

My Conclusion…For Now

As it stands right now, I’d be inclined to agree that pre-menopausal (and perhaps peri-menopausal) women are more likely to have poor—or at least different—experiences with intermittent fasting (at least as a weight loss tool). That said, it appears to be a potentially gender-neutral therapeutic tool for chemotherapy, cancer, and age-related neurodegeneration patients.

So, Who Should and Who Shouldn’t Consider Fasting?

Have my recommendations changed?

If you haven’t satisfied the usual IF “pre-reqs,” like being fat-adapted, getting good and sufficient sleep, minimizing or mitigating stress, and exercising well (not too much and not too little), you should not fast.

These pre-reqs are absolutely crucial and non-negotiable, in my opinion—especially the fat-adaptation. In fact, I suspect that if an IF study was performed on sugar-burning women versus fat-adapted women, you’d see that the fat-burning beasts would perform better and suffer fewer (if any) maladaptations.

I would also caution against the already lean, already calorie-restricted woman jumping headfirst into IF. I mean, fasting is ultimately sending a message of scarcity to your body. That’s a powerful message that can get a powerful response from our bodies. If you’re already lean (which, depending on the degree of leanness, arguably sends a message of scarcity) and restricting calories (which definitely sends a message of scarcity), the response to fasting can be a little too powerful.

I’d also say that daily fasts, a la 16/8 or even 14/10, run the risk of becoming chronic stressors and should be approached with caution by women. Same goes for ultra-long fasts, like a 36 (or even 24) hour marathon.

Most of all, however, I’d simply suggest that women interested in fasting be cautious, be self-aware, and only do so if it comes naturally. It shouldn’t be a struggle (for anyone, really). It shouldn’t stop your cycle or make it harder for you to get pregnant. It should improve your life, not make it worse. If you find that fasting has those negative effects, stop doing it. It should happen WHEN (When Hunger Ensues Naturally), if it happens at all.

Some Warning Signs To Watch For

  • Weight Gain (especially in the midsection)
  • Insomnia
  • Muscle Loss or Reduced Performance In the Gym—It’s perfectly reasonable to suffer in the gym on fasting days, but watch out for persistent strength losses. If your fitness and strength levels are consistently trending downward, fasting may not work for you.
  • Infertility
  • Loss Of Your Period—Skip meals, not menstrual cycles.
  • Excessive Hunger—Feeling peckish is good for everyone and makes food taste better; constant satiation is a trap of modernity. But you shouldn’t be ravenous. Thoughts of food shouldn’t consume you.

The good news is that most of the ill effects of fasting are blatant and conspicuous. They don’t hide. They don’t lurk in the background. They’re really hard to ignore—so don’t!

Some Thoughts For Women Who Want to Fast

Instead of aiming for the longest fast you can tolerate, aim for the shortest fast that gives results. Don’t try to power through a 24 hour fast, braving headaches and foggy thinking and overpowering hunger. Do try eating dinner earlier so you get a good 12 hours of “fasting” simply by going to bed and eating breakfast at a normal time.

Don’t fast unless you have a good reason. Good reasons include:

  • Having significant amounts of fat to lose.
  • Your oncologist giving you the go-ahead to try using it to improve the effects of chemotherapy.
  • Your neurologist giving you the go-ahead to try using it to improve brain function in the face of cognitive decline or dementia.

Bad reasons include:

  • Keeping the pregnancy weight at bay.
  • Going from 15% body fat to 12%.
  • To boost your 5x weekly CrossFit sessions.

Men and women have inherent metabolic and hormonal differences, and it’s evident that these differences in part determine how we respond to a stressor like intermittent fasting. I’ve never prescribed intermittent fasting as a requisite piece of the Primal lifestyle, but rather as an elective addition, a personal choice—only as a potentially therapeutic strategy that each individual must test for him or herself. 

I generally fast when it makes sense – if I’m traveling and good food isn’t available, if I’m just not hungry, stuff like that. I periodically do 16/8 or 14/10 (i.e. eating in an 8 or 10 hour window) and find it works great for me because I am fully fat-adapted. But even I don’t hold rigidly to that. It’s not for everyone. And that hasn’t changed.

That’s it for me, today. What about you? If you’re a woman who has tried fasting, or know someone who fits the description, let us all know about your experiences. I’m intensely curious to hear from as many of you as I can. Thanks for reading.

By the way…because this is an updated version of a previous article (as I noted at the beginning), previous comments will still display. Keep in mind they may refer to the context of that previous article version. 

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