Dear Mark: ApoE4, Red Eye Recovery, TEDx Paleo Debunking, and Cough Drops

It’s Monday, which means it’s time for another edition of Dear Mark. This week, I’m covering four reader questions. First up is a really tricky one: ApoE4, the ancestral allele that’s classically associated with a host of maladies, like cardiovascular disease and Alzheimer’s. What’s the deal with it? We don’t have any concrete answers (yet), but I give my take on it. Next, I tell a reader who’s flying to Chile for vacation how I recover from travel-related sleep disturbances and realign my circadian rhythm. After that, I cover another paleo debunking that’s actually not much of a debunking, this time a TEDx video from Christina Warriner. And finally, I explore the eternal question of Halls cough drops, including whether or not any natural alternatives exist.

Let’s go.

Hi Mark and Worker Bees,

I read that APOE4 is the “ancestral” allele for the APOE genes. It is the risk factor for Alzheimer’s. I find it hard to believe that checking out mentally is in any way desirable. You linked a few months ago to an interesting article about high-carb seniors succumbing to cognitive impairment. Might you be able to think aloud about this topic?


ApoE is apolipoprotein E, the string of amino acids that attaches to lipoproteins and allows them to cross the blood-brain barrier and get into the brain to deliver nutrients and cholesterol and remove toxins. If a lipoprotein has the ApoE marker, it will be allowed into the brain to do its work. Different genetic variants of ApoE are better and worse at this task, however.

ApoE2, is associated with a lesser risk of Alzheimer’s and ApoE3 is “neutral.” Meanwhile, ApoE4 is associated with higher total cholesterol and a greater risk of Alzheimer’s. Thus, most people assume that the high cholesterol is also causing the Alzheimer’s and dementia. It’s not quite so simple, of course.

Brain is perhaps the richest source of cholesterol in all the land (or sea); just an ounce of raw lamb brain contains nearly 400 mg of cholesterol. In fact, brains – living ones – need plenty of cholesterol to work right. The synapses, or connections between neurons, are made of cholesterol. In case our brains aren’t getting enough cholesterol, the astrocytes – brain cells which supply nutrients to neurons – can even manufacture their own cholesterol.

That may explain why statins can hamper brain function, why high cholesterol late in life is associated with a reduced risk of dementia, and why Alzheimer’s patients have lower levels of cholesterol, phospholipids, and fat in their cerebrospinal fluid. Clearly, our brains need cholesterol.

So why is ApoE4 associated with high cholesterol and Alzheimer’s?

One hypothesis is that people with ApoE4 need higher baseline plasma lipids because ApoE4 makes the brain less efficient at taking up cholesterol. If that’s true, high cholesterol may be a protective mechanism designed to overcome this limitation. This would jibe with the observation that Alzheimer’s and dementia are often preceded by a big drop in cholesterol. That is, the early, asymptomatic stages of Alzheimer’s are associated with a decline in serum total cholesterol, not a rise. Interestingly, young ApoE4 carriers have better memory, better learning capacities, and more neural efficiency in general than non carriers, so it’s not all bad. Something goes wrong down the line.

My take is that ApoE4 carriers, being “ancestral,” are simply more susceptible to neolithic stressors like tobacco (yeah, yeah, I know it’s been smoked for a long time, but not in its current form), heavy metal toxicity, sedentary living, and chronic stress. Some evidence:

I’d also guess that a bit of intermittent fasting, or at least a movement away from the wholly modern grazing method of eating, would also be helpful. At any rate, closer adherence to a Primal way of life appears especially crucial for ApoE4 carriers.

Another view is that ApoE4 carriers are actually more sensitive to dietary fat, particularly saturated fat, as well as carbohydrate. William Davis MD has found that for these individuals, moderation of both fat and carbs is necessary to avoid elevations in the number of LDL particles, particularly small dense LDL. ApoE4s should probably at least monitor their lipids and spring for the more advanced tests to note how fat and SFA affect LDL-P, LDL-C, and small dense LDL – just to be safe.


I’m leaving for a vacation to Chile later this week and I’m facing 2 overnight flights within 10 days of each other.

I’m about 6’2″, broad shouldered, and for the time being my pocketbook precludes me from sitting in the pointy end of the plane.

This upcoming flight has me wondering what tips and/or advice you have for people who are facing a situation with non-ideal sleeping conditions? What can be done in advance from an exercise/nutrition/supplementation standpoint to partially mitigate the effects of poor sleep?

Also, do you have any suggestions for things that can be done to promote better sleep in a tight spot (no pun intended!)?

Thanks for everything you do with this site. Look forward to your suggestions.


As a frequent traveler, I’ve figured out a perfect regimen for getting my clock aligned with wherever I’m staying. It may not work for you, but it certainly does for me and pretty much everyone else to whom I’ve suggested it.

On overnight flights going East, you’ll be experiencing what amounts to two “shortened days” as you erase multiple time zones from you diurnal rhythm overnight. Set your watch to your new intended time zone when you are in the air. Get as much sleep as you can on the plane. Typically you’ll arrive sometime later in the day at your destination, so you won’t have to work hard to stay awake, but do so. You got 4-6 hours on the plane maybe, but the new “day” will be several hours shorter. Adapt your mindset to the new time zone immediately. Do NOT nap. I usually go for a short walk to explore the city or I hit the gym and ride the bike a bit. As it gets close to the new bed time, try to take 3-5 mgs of melatonin an hour before your intended bedtime. By the time you hit the hay, it will have done a decent job resetting you internal clock and allowing to get some regular zzz’s. Repeat the melatonin ritual the next night and then cut in half the third night. From there you should be good to go.

Now, for Westbound flights that follow the daylight most or all of the way, you will be experiencing a very long single day and usually arriving towards the end of that day. In this case, same thing, set your watch on the plane to “get into” the new time zone. Stay awake as you see fit, but try to take a long nap maybe halfway through the flight. You will have rested, but not have had too much sleep that it throws your normal night off. When you arrive, same process, stay awake until it’s the local bedtime, find things to do, take a hike or work out, and do the same melatonin ritual.

Finally, for long night flights, just get as much sleep on the plane as you comfortably can, because you’ll have a long day at your destination. I try to do two naps with a few movies in between.

To sleep on the plane itself, I have a few suggestions:

Get a window seat. I know the aisle offers more legroom, but it’s hard to get comfortable when you have to worry about where to put your head. With a window seat, you can wedge yourself up against the side of the plane. Plus you won’t have people crawling over you to get to the bathroom.

Get an exit row. More legroom is always better.

Consult Seat Guru. Figure out what model plane you’ll be on and then check reader reviews to find the best seat in the house.

Bring a pillow if the airline doesn’t provide one. I like a super compact backpacking pillow, the kind you’ll find at REI. Barring that, a rolled up article of clothing works.

Hey Mark, big fan of this site.

Have you seen this TED talk by Christina who claims to debunk your theory and other Paleo like diets? She does a lot of fad calling, showing your books and movement a fad.

Check out the talk when you have the time and please, as your readers, we’d all like to see a post on your thoughts around this. She has left a lot unsaid and I’m wondering if she’s even read any of the books she’s talking about.


I have seen it. It was better than Paleofantasy, but it suffered from some of the same mistakes. Mainly, she didn’t really do her homework and ends up promoting a fairly Primal way of eating without actually realizing it. It’s just that the first five or six minutes are really rough.

She begins by saying that humans have no anatomical or physiological adaptation to eating meat, meaning (I assume) because we don’t have big scary claws and teeth and the ability to overpower and devour a bison barehanded, we aren’t “meant” to eat animals. On some level, this makes sense. Dogs, cats, lions, tigers, and other fearsome predators all come equipped with the physical, mechanical equipment to break down and consume a carcass. Humans do not. We do, however, have technology. We have spears, stone knives, bows, atlatls, slingshots, and, now, rifles, to kill and butcher our prey. We’ve harnessed fire to cook it. We’ve also harnessed fire to cook starch, which – unlike meat – we actually have to cook in order to really digest. Why no mention of that in the video?

That said, despite the pretty obvious vegetarian bias (“paleo is for men,” “paleo is all about meat,” etc), the rest of the talk is good. She ends by acknowledging that we can learn a few things from paleolithic nutrition: eat fresh foods; eat whole foods; and eat high species diversity. Oh, and don’t eat refined sugary drinks. I agree with her on all these points. I think if she read through this blog she’d agree with most of mine.

Robb Wolf gave a good minute by minute summary (a Wolf’s Eye View) that I’d recommend reading. I agree with everything he says in it.

Dear Mark,

I have need for a cough drop for nighttime sleeping or when attending an event requiring quiet. I just looked at the ingredients in the 5 bags of Halls my hubby bought and it’s almost all sugar and junk. What would you recommend especially now that I’m on 21-day Sugar DeTox? Help!  🙂
Currently, I have 2 cloves of clove in my mouth guessing this may help!  ??



I wasn’t really able to find any natural cough remedies with strong evidence. If natural methods aren’t working, a single Halls cough drop only has about 4 grams of sugar, mostly glucose (from glucose syrup). Unless you’re really wedded to this 21-day detox, I’d say just go ahead and take the cough drop. Besides, the 21-day sugar detox is more about avoiding sweets – elective junk food – than eliminating every trace molecule of sugar, which in this case is primarily glucose rather than fructose. One study even found that both menthol and a sweet taste are effective at suppressing coughs, so combining the two is likely more effective than either alone.

A bad night’s sleep is way, way more detrimental to your health than a tiny bit of sugar:

And those are just a few examples.

Both honey and chocolate may be effective against coughs, but, well, those aren’t exactly sugar-free.

That’s it for today, guys. Thanks for reading and be sure to chime in with your thoughts/opinions/suggestions in the comment section!

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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112 thoughts on “Dear Mark: ApoE4, Red Eye Recovery, TEDx Paleo Debunking, and Cough Drops”

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    1. 23andme is only $99, and that’s one of the SNPs they check.
      It’s interesting stuff.

  1. I have to agree that chronic messed up sleep is far worse then a little sugar. If it were me I would set the detox aside, eat right and focus more on sleep, then when the cough is over with go back to the detox so it can be combined with solid nights of sleep. I imagine the end result would be much healthier.

    1. Very Good way to put it. Good sleep and no sugar has to be much better than just no sugar. Chances are not so good sleep will cause a huge craving for sugar!

  2. As far as flights go, I figured out on my own what Mark recommended. Depending on where and who you’re flying with, you will have a TV screen all to yourself. I get a window seat, and set my watch to where my FINAL destination is, not any of the intermediate hops. I then sleep or force myself to stay awake (by watching movies, reading a book etc.) per the destination’s time zone.

    I had almost no jet lag doing this going both east and coming back west.

  3. Trying to debunk paleo is like trying to make mother nature your bitch. Good luck with that! She does not care about what you want or your agenda.

    1. I’m late to this post – LOVE your reply!

      Yes, she doesn’t care about your desire to be a hip, tree-hugging, compassionate vegan or what-eh-ver! Go Mother Nature, Go!

  4. Hey Mark,
    I am going from the West Coast to Europe this summer–a very long flight that requires quite a bit of sitting. Any advice on how to remedy the ‘stuck-in-a-seat-for-12-hours’ issue associated with flights? I usually just walk around the aisles like a crazy person because my butt starts to hurt from so much sitting.

    1. A couple of comments from a former frequent flyer… There is no remedy for being stuck in a sardine-can seat for 12 hours. If you have a brief layover between connecting flights, try to walk around the airport as much as you can or find someplace out of the way where you do some loosening-up exercises. Otherwise, about all you can do is squirm a lot or, as you said, walk up and down the aisle–probably to the annoyance of the person seated next to you.

      As for the idea of requesting a seat in an exit aisle for more leg room, somebody has to be physically capable of opening the exit door in the event of an emergency. It could end up being you. If you aren’t up to managing that, it might be better to sit elsewhere.

      1. A few years ago, I was on a trans-Atlantic flight that had a laminated card with in-flight exercises illustrated. It was pretty funny – they tried to mimic the graphic style of the emergency-procedures card while providing a few good tips for stretching and maintaining good blood flow while seated for several hours. I can’t remember the details, but the exercises involved as much movement of joints (neck, shoulders, spine, arms, legs) as possible along with some muscle stretching. I think it even had a warning about not elbowing your neighbor in the face while stretching.

        Also, drink lots of water. The air in an airplane at high altitude is exceedingly dry.

    2. I have to fly to China from Los Angeles (~15hr flight) on approximately a quarterly basis for business. Here are my key tips:

      1. Wear some graduated compression socks. I have found they make me feel better on arrival. They also have the larger benefit of helping to prevent DVT (Deep Vein Thrombosis).
      2. Stay hydrated – bring an empty water bottle through security and have the flight attendant fill it up in flight. (Most airlines will offer water throughout the flight, but a water bottle is a surefire way to have water when you want it).
      3. Walk around as much as you want/need. There is usually more room near the galleys where you can stand/stretch without disturbing too many people. Squats are particularly effective for me since they engage the glutes that have been inactive for hours. You will notice that a lot of people will copy your routine.

      1. Hi…like your suggestions but as a flight attendant might I give my take? The galley is my “office” and “workspace” not the spa. If you come to squat, stretch, etc.don’t stay forever. We are busy and workspace is limited. Sometimes we even get a chance to eat…don’t watch and stick around. As for water bottles. We have limited supplies…thesupply truck can’t reach us up there…

      2. We’ll do water bottles but can’t always accomodate full bottles or several refills. There are usually full planes these days. Actually it’s not sanitary to refill used bottles…and it’s really not supposed to be done but we do our best.

  5. We have spears, stone knives, bows, atlatls, slingshots, and, now, rifles, to kill and butcher our prey. We’ve harnessed fire to cook it.

    … but but agriculture invented by man in the same time frame is bad?

    I guess man has had enough time to evolve to eat cooked speared butchered meat? Come on! Bendable arguments galore!

    1. Weaponry and fire predate agriculture by many, many, many thousands of years. Stone tools from over 2 million years ago have been found. Fire has been used over a million years. Agriculture is not even in the same ballpark.

      1. Yep, tool use is the key definition of the paleolithic period. Evidence goes back, as Mack Daddy says, about 2 million years. And those early tools were either hunting weapons or carcass-processing tools. Agriculture in any measurable form started showing up about 12,000 years ago, which I think is the defining point of the neolithic period.

      2. Not correct! Fire is definitely not being used on a regular basis by humans that long ago. We are looking more at 400,000 years ago for regular use of fire. Even so, this is well ahead of the advent of agriculture. There is no need to exaggerate. This link is just one of many that refer to actual research on the subject.

        1. Thanks for the link! I always like to hear about our ancient ancestors. My bad, I just never heard that before.

    2. Are strawmen paleo?

      Both the ‘but agriculture invented by man is bad’ and the responses to it miss the point. Agriculture isn’t the problem. Making cereal grains the staple of the diet is the problem. Grow all the leafy greens you want.

      1. Piper – I think we wrote up our responses at the same time, but I totally agree.

      2. I agree with your take on agriculture being just fine if the right crops are grown in the right way, but a fair-minded interpretation of Mrak Darly Arple led me to address the argument that we evolved to eat certain foods. If we evolved to eat different foods due to more efficient hunting, and due to cooking, then perhaps we also evolved to eat different foods due to whatever changes in our diet would be caused by agriculture or animal husbandry. Thus, it becomes relevant to compare time frames. Mrak Darly’s argument isn’t an intentional strawman if Mrak Darly believes that all the things he listed happened around the same time.

    3. Unfortunately, usually the only serious bending of arguments comes from people pretty desperate for the idea can eat anything we want because we’re more civilized than the animals we see around us or some such nonsense.

      Farming is not “bad”, it’s just different and not ideal nutrition. Modern grain farming has taken different to whole new level and is far less human friendly than even 100 years ago.

      And as noted, farming comes much, much later in our existence as a species. It’s almost a rounding error.

      But whatever. Meat equals bad and there’s got to be some way to justify that view.

  6. The ApoE4 overview was excellent; thanks. My grandmother lived with Alzheimer’s for about the last decade of her life; a sad degenerative process to behold. A better understanding of the triggers is at least hopeful. For her I suspect it was the chronic unexpressed grief that raised her cortisol levels over the preceding few decades which added to any potential genetic burden she may have carried and it has certainly caused me to focus on living now, and letting go, to reduce stress where possible. I’m sure by attending more to the spiritual and emotional state we can have a greater effect within epigenetics.

  7. Jo didn’t mention what’s causing the cough. A cool mist humidifier near the bed might help if it’s allergy-related. If it is from a cold, you could use one of those plug-in menthol things or a steam vaporizer with menthol liquid or just Vick’s Vaporub on the chest. Rooibos tea can be soothing. Also, there’s a spray called Singer’s Saving Grace. I think it contains alcohol, though. Is that allowed on the 21 Day Sugar Detox?

    1. I was thinking the same thing. I had a terrible cough and general “drippiness” from age 12/13. Dr after dr told me I had postnasal drip, but couldn’t tell me what to do to alleviate it. I took benadryl all the time to try to control it. Once I eliminated wheat and corn from my diet, it went away for good. The only time I get it anymore is when I have a fish taco (cornmeal coating, corn tortilla) or eat a “gluten free” treat from a friend who doesn’t know about my sensitivity to corn…

      1. same here. post-nasal drips, earth-shaking coughs and colds that lasted for weeks. most days woke up gagging on mucous. lovely. my normal. all my life.

        eliminated grains and haven’t had a sneeze or sniffle in almost 4 years. even when my b/f gets sick or crud goes around work? i remain fit as a fiddle.

      2. One of the best health changes I have made in the past five years is starting regular sinus washes during allergy season. I was a daily Allegra popper with a persistent sinus infection from September through April until I started using a daily sinus wash. Within weeks I no longer needed any allergy medication! After cutting the wheat out last year, I have noticed my residual symptoms vanishing as well.

        My personal fave is the soft squeeze bottle variety. The learning curve is a little scary the first time, but it is truly a soothing and helpful thing to do. I am a sinus wash convert for life!

  8. I don’t understand how some of these anti-paleo people basically don’t do any research at all, despite being obviously quite educated. I had a better concept of paleo and primal after the first hour of researching it and I wasn’t about to give a TED talk.

    On a side note, I’m not stuffing myself with meat at all. My eat consumption is maybe up 20% since going primal. It’s not like I’m having two steaks for every meal as this TED talk seems to imply.

    1. Well, in fairness, if you are vegetarian (and it sounds like the speaker is), the meals look like meat plus vegetables on the side. (And that’s what it is day to day.) For most people on SAD, it’s simply subtracting the poor nutrition and excess calories from the plate and calling it a day. It’s a bit of a nightmare, however, (and looks “excessive”) from a vegetarian POV.

      I don’t know how meat consumption became “bad” and male. (Or how that became “bad” either.) I’m trying to remember which country star had “Real chicks eat meat” printed on her T-shirt. I feel like I should print up a few thousand and just give them out.

      I’m sorry, my femaleness is just not intertwined with going “ewww, gross” when confronted with the gift of nourishing food.

      I know Mark and many others try to hold out olive branches to the vegetarians. That’s the right thing to do. However, I don’t think there’s any escaping the fundamentally different POV on diet and food the two communities have.

    2. Take my wife……fixed mindset…brainwashed by CW, no imagination,only up to 21 inches

  9. chronically sleeping with a lump of sugar (cough drop) in your mouth will wreak havoc on your teeth, however.

  10. Regarding the TED talk trying to debunk paleo eating: She didn’t mention the original Inuit/Eskimo diet which was nearly all meat and fish–almost always eaten raw, though. They had some roots and berries and maybe lemon grass in the summer but for nine months of the year it was meat and fat and fish. So why didn’t they get scurvy from lack of vitamin C? (She brought up the vitamin C issue early in the talk.) The fat of the whales and seals is loaded with vitamin C and they ate a lot of that.

    Also, the artic explorer, Vilhjalmur Stefansson, who spent seven years with the Inuit, came back and told people that they didn’t need fruits and vegetables. The medical community put him and another artic explorer to a test. They ate only meat, under supervision, for one year. (1920’s, organic, pasture raised.) They were perfectly healthy after that year.

    1. Oops! I forgot to mention, the Inuit/Eskimos had little to no obesity, cancer, heart disease, and diabetes until they started eating a western type diet.

  11. I would invite her to give a talk in Ancestral Health Symposium. I would love to see see how she would deal with some solid “to the point” questions there. And that’s her real challenge. I am pretty sure she would be ignored rather, and not because what she is saying is wrong but what she has is the concept of Paleo Nutrition in its infancy during the 1970’s. I guess things are more clear than that now.

  12. “We have spears, stone knives, bows, atlatls, slingshots, and, now, rifles, to kill and butcher our prey.”

    And before these, we had savvy. Google “Bushmen stealing meat from lions” for one of the most amazing videos you will ever watch.

    1. The 65-year-old leader in this clip looks and moves like a young man!

    2. * correction – San not Sand.

      See also videos of San hunting large animals by running them down. True, they finish the animal off with a spear, but that is a coup de grâce. They could use a rock or whatever, or wait for it to die.

      Also, as Mark has frequently mentioned, meat does not necessarily mean large game animals. It also includes small birds, bugs, snails, and lots of other creatures. And certainly our ancestors have always eaten eggs.

    3. Agree. Finished a book called “The Old Way: The Story of The First People” by Elizabeth Marshall Thomas. It was a fascinating story about the Bushmen of the Kalahari. What was amazing was the respect that humans and lions had for each other. They understood each other.

  13. Can we please have someone (Mark?) to do a TED-lecture “Debunking the debunking of the paleo diet.”

    1. I think what’s needed at this point is a formal debate – with several esteemed folks on both sides of the issue, up on stage at the same time, with a neutral moderator. Not so much so there can be a winner and a loser, but to present the various positions, arguments, and counterarguments in the same place, so they can be heard and considered together – rather than scattered here and there on blogs and in books and other writings.

      1. They have been doing exactly that on NPR. Formal debates on different dietary perspectives, including paleo and low carb..too bad NPR doesn’t get as much coverage in mainstream media.

    2. Why would you even care what other people think? All that matters is whether it works for you personally.

      People sometimes notice that I don’t eat sweets, grains, or dairy (except butter), but I don’t make a point of mentioning that I eat a paleo diet. As far as I’m concerned, the debunkers can have a field day with their erroneous information. It doesn’t affect me.

      1. Thank you Shary for pointing this out, I should be wiser, too. I just realized that it stresses me out to hear people talking about how they can’t eat butter because it shoots their cholesterol up etc etc (while obese and allergy-ridden nonetheless). I was just looking at them during the lunch break, with a plate of steamed broccolette patted with lots of butter and roasted pork on top, in front of me, All I did was roll my eyes, but inside… I should just not pay attention, they will not change and this doesn’t affect me at all, let them be.

  14. I love Traditional Medicinals Lemon Echinacea Throat Coat tea. Several tea brands carry a throat-soothing variety, and they are really helpful. Got me through the flu and bronchitis this winter.

  15. Mrak,
    I don’t believe you are understanding the time frame we are talking about.

  16. Mark’s suggestions sound great. What worked best for me on those overnight North America to South America trips was to get a window seat and start sleeping 8 – 9 hours before landing. Those arrivals tend to be pretty early and you will probably awake around 30-45 minutes before landing with the increased activity on board as well as the announcements. The most rhythmically disconcerting thing for me was the overnight change in number of hours of daylight/dark. It still took a couple of days each way to adapt to that.

  17. I think it is interesting to see things like the TED talk. As paleo grows in popularity, so too will its detractors. What is funny is that they’ll never probably go after the ACTUAL central components of nearly all paleo diets (eating whole, natural foods; avoiding refined sugars and byproducts) and attack the more “sensational” and eye catching ones (No grains! low-carb, high fat!)

    1. They always go after the CrossFitter’s “something to prove” model of Paleo and not the “just eat real food” actual model.

  18. I’ve stumbled across loquat extract as a treatment for cough and phlegm. Ialso swear by the Ricola original recipe cough drops, since their ingredients are largely just sugar and herbal extracts, rather than the more “medicine-y” drops.

  19. Regarding Jet-Lag

    I travel to Europe and India occasionally for work and what Mark says is spot on. In addition to the melatonin, naps, etc, be sure to get as much natural sunlight during the morning or day as you can. Face the window at breakfast, and I even move my furniture around to face the window if I’m working in the hotel in the daytime (lift heavy things!). It has something to do with blue light and special receptors in your eyes, but I can’t remember the details. Also I have used binaural sleep tracks and guided meditation tracks when really fighting the jetlag monster.

  20. Thank you for addressing the ApoE4 question in your typically thoughtful fashion. The links embedded in the article are terrific, too. Again, Thank You!

  21. Good article overall, but I especially enjoyed your discussion on jet lag. I’m a pilot and cross the Atlantic frequently, and as you correctly stated, the eastbound leg is the toughest. My strategy is to take a short nap when I get in, no longer than an hour or two. This takes discipline, but is crucial to staying on track. Next, I get up and do my sightseeing, have a nice dinner and a beer, and get to bed at a normal time, say 9-10 Pm local time. I get a good night’s sleep and get up in the morning fresh for my return flight back to the USA.

    1. My husband is a FIFO worker, and flies every 4 weeks across Australia. We have noticed that this routine has affected his health, and we are conscious of ways of alleviating stress. One of the positive things is buying noise cancelling headphones which make listening to music and movies much more relaxed, and when he just wants to doze, they simply cancel out the jet noise. These days they are not too expensive, but I would favour the cushioned ones over the ear buds as they are more comfortable and effective.

  22. There’s a simple solution to the cough-drop problem. Use mints sweetened with xylitol. They’re not only sugar free, but actually beneficial to dental health. I widely available brand is Spry.

  23. “Researchers from the Cleveland Clinic have discovered it’s not the saturated fats or cholesterol from a fatty steak that’s triggering heart problems, but a chemical process involving gut bacteria and a compound found in meat called carnitine that may be to blame.”

    This news article is all over the internet, I hope Mark will address it at some point in the near future. I’ve been taking an l-carnitine supplement, think I will stop for now until I can get some more information.

    1. It was also discussed briefly in yesterday’s comments. I told my husband to stop taking the supplement too. I actually believe that for most supplements with only very few exeptions it is too much of a good thing can actually be bad.

      1. Yes, and professor Lora Hooper, who follows the Paleo diet, said “YIKES”. I thought the article pointed out more about TMAO than carnitine. Anybody out there know something about the TMAO in Red Meat? I wrote Mark an email asking if he could comment on this.

        1. +1, I hope Mark discusses this. This study appears to be backed by science, instead of the usual observation/correlation.

  24. I wouldn’t worry about the sugar in cough drops as long as you aren’t popping them as fast as they dissolve.

    real Licorice, many forms of mint, sage, menthol… you could probably make fairly “clean” versions of soothing candy yourself.

  25. Check out the link to Robb’s minute to minute summary of the Ted talk. Good stuff. I think we are now mainstream with Paleo/Primal since the attacks are coming in hot and heavy, with the ever present Conventional Wisdom crapola.
    Let’s welcome them…I’ve never belonged to a more knowledgable (and healthy)group of thinkers!

  26. Chile is only an hour ahead of the east coast, so assuming the reader is coming from mainland US, the trip is primarily southbound (not east or west) and jet lag shouldn’t be too bad. Looking back at his post, he wasn’t even asking about jet lag, but just about trading a night in a bed for a night in an airplane seat.

  27. Oh, wow, I watched her video and she is definitely promoting going primal. Eat fresh food that’s locally available, eat offal and bone marrow, avoid sugar and processed foods because they only have three ingredients and Override our body’s mechanisms to signal fullness and satiety!! very good! oh but don’t say you are paleo/primal/neanderthin because its a fad!

    1. Nope she’s not. Most people on this site, including the author, are contrarians so they wouldn’t appreciate it, but she’s looking at the other side of the argument. Truly intelligent people are open minded and listen to other side of the argument, check every point and decide which is feasible and which is not.

      All nutritional science will argue against consuming highly refined foods high in fat salt and simple sugars like chips, sugar drinks, burgers and white bread. The dietary recommendations support the consumption of whole foods. But this includes wholegrains and cereals and complex carbohydrates, that have undergone less processing. Along with vegetables, fruits an moderate amounts of dairy (one food where more processing- to remove the fat and add ca++- is better). Most of out chronic health problems are cause by society’s poor adherence to national dietary and physical activity guidelines. Not the existence of them. Most people stick them in the ‘too hard basket’an leave them there.

      What she’s saying is Paleo is not the be all and end all of all diets. It’s a fad out to make money. Given no one even knows what it is and it is impossible to emulate today. There is not enough evidence to support just binning 60 years of peer reviewed literature (most of it is commercial books and blogs and a handful of journal articles that do not qualify as comprehensive studies) for something that’s logistically impossible.

  28. RE: Jet Lag – if I can help it, I never fly overnight. I used to commute from the West Coast to the East Coast and whenever I attempted the red eye I’d end up with run-down-itis. If I can spare an extra day to fly in and get in synch with the local time zone, it was worth the expense. “Fly East to Party, West to WorK”

    1. Fly East to party …. West to work; as a flight attendant I have to remember that 🙂

  29. Regarding the need for a cough drop at night (or whenever): I have had low-level coughing and congestion for as long as I remember. Since going Primal, it’s much better. However, it still hangs around from time to time.

    I just recently started taking a Spirulina supplement from Mercola and it seems to be helping a lot! Hardly a cough or need to clear my throat in a week! There’s even a study showing it helps:

  30. “I read that APOE4 is the “ancestral” allele for the APOE genes. It is the risk factor for Alzheimer’s. I find it hard to believe that checking out mentally is in any way desirable”

    I try to mentally check out at least once a day! 😀


    Combination of apolipoprotein E4 and high carbohydrate diet reduces hippocampal BDNF and arc levels and impairs memory in young mice.

    And Chris Masterjohn: It makes sense to increase our consumption of fresh fruits and vegetables, saturated fats, and sources of DHA such as egg yolks from pastured chickens and cod liver oil, and to decrease our consumption of carbohydrates and most polyunsaturated fatty acids. A high-fat diet may help by preventing insulin resistance and by contributing neuro-protective ketone bodies as well.

    A high fat (ample saturated fat) diet reduces the requirements for omega 3 fats, and preserves the omega 3 fat stores better than other diets. Ketogenic diets have been shown to be protective against various neurodegenerative diseases.

  32. Jo- The “cough drops” that have always worked the best for me and are usually a much better alternative to the usual stuff (Halls, etc) are slippery elm lozenges. You can find the Thayers brand at almost any drug or grocery store. They’re much less sweet than any other cough drop I’ve tried, and they just seem to work so well! I also enjoy the taste, which is pretty subtle compared to kick-you-in-the-face menthol.

  33. Oh, I was hoping you were addressing actual red eyes… I don’t have to fly to suffer. I suspect either allergies or insomnia, especially since I have some dark circle issues too, but any insights would be welcome!

  34. I like Zand menthol herbal lozenge or their Elderberry-Zinc lozenge. They have other flavors, too. I got them at a natural foods store but you may find them on Amazon. The first ingredient listed is brown rice syrup, which is basically sugar, but the rest is things like slippery elm, horehound, licorice, etc. They are corn-free and free of artificial colors, flavors, etc. They have a tropical soother for sore throats that is good, too.

  35. About the cough – you might want to check out doTerra oils. They are certified pure therapeutic grade and completely natural, only made from herb and plant extracts. We use Breathe and Peppermint and a good one for colds is On Guard.

  36. As the creator of the program I thought I’d chime in here for anyone interested in what I’d recommend on The 21-Day Sugar Detox for a cough issue, it would definitely be the following:

    1- herbal tea, specifically I like some from Traditional Medicinals like Throat Coat and Echinacea Plus

    2- a humidifier for sure – I like a warm air one personally, but it may depend on the season.

    I do wonder why this person “needs” cough drops, however. If it’s a matter of a cold, that’s one thing, but it almost sounds like a chronic issue. If that’s the case, I’d look at his/her overall hydration level as well as gut health and fatty acid digestion. It’s pretty common for skin and mucous membranes to feel more dry if these areas are not optimized.

    While on The 21DSD or otherwise, I wouldn’t recommend a commercial cough drop. I like some of the natural varieties that include slippery elm and possibly honey as ingredients. Glucose syrup may be derived from wheat, so I’d steer clear.

    Diane @ Balanced Bites, author and creator of The 21-Day Sugar Detox program

  37. i was waiting for mark to tell the traveler to walk around barefoot to ease jetlag!

  38. I have had intense periods of intercontinental flights (all 5 continents and back) and have tried everything. As I see it, the biggest problem is that you are tired when you shouldn’t be. My advice is to sleep whenever you can for as long as you can (6 naps a day? Fine). You will be up at odd times and it will take a few days to get your schedule straight no matter what but you won’t be tired. And if you are not tired, you can work and enjoy yourself.

  39. That you for your post. It is great as usual. I have a good tip for you for coughing: put a warm compressor on your chest at least once a day and drink a cup of hot tea with herbs. This method always saves me from coughing.

  40. The second part of the TEDs video is very interesting. As for “seems to be targeted at men”, although I’m aware that more than 50% of Paleo adepts are women, the marketing materials and images on the paleo sites are indeed mostly men. This might be because the main Paleo sites and blogs are written by men, but it would be great to see more images of women or rather equal representation of women in the materials.

    1. Carrie’s new Primal Woman book ought to help with that bias too. I know there are lots of women from all kinds of ages and backgrounds who are finding their health turning around as they swap their no-fat, splenda-sweetened yogurt and low-fat cereal with skim milk for a plate of bacon and eggs. I know mine has!

  41. Mark, thank you for posting this on apoE4 and Alzheimer’s and especially all the links. It pulls together a lot of things that I can see happened in my father’s life in the couple of years before he was diagnosed with Alzheimer’s. I have no idea if he has the apoE4 allele but his basic diet used to be fairly basic meat and two veg, including an almost daily bone broth and very few sweet things. Then all around the same time, he became more sedentary – attempting to heal a detached retina – and his diet became more CW as my mother took over the shopping.

    I’m trying to move him back to a more primal diet now, as removing wheat (all grains in fact) has already made a noticeable improvement in his cognitive ability. Looks like getting him into walking again will be another good move. He only needs another 7 years now to get a telegram from the Queen!!

  42. “One hypothesis is that people with ApoE4 need higher baseline plasma lipids because ApoE4 makes the brain less efficient at taking up cholesterol. If that’s true, high cholesterol may be a protective mechanism designed to overcome this limitation.”

    I just recently found out I am ApoE3/ApoE4. This was my guess when I read the description of it, knowing how important cholesterol is to the brain. But even people with 2 copies may go on to never develop Alzheimer’s. And, even though we don’t hear about it – it’s not news unless it involves drugs – there is ongoing research using a high-fat, high-cholesterol diet to help Alzheimer’s patients – they have made progress. I haven’t seen the studies so I can’t link anything. This is info from the Alzheimer’s forums at 23andMe. I’m just so happy I figured it out.

  43. Cough Drops.
    I frequently get spasmodic coughs. I use Thayers Slippery Elm Lozengers. They taste awful but work. The cherry flavor has .10 g(1/10) of dextrose/sucrose. I don’t know what the original flavor(none) contains.
    Natural or health food stores and some of the larger pharmavcy chains carrythese.

  44. I’d appreciate Mark’s take on the L-carnitine study mentioned in the above comments, too. Thanks.

  45. I think you should do a TED conference somday, maybe debunking “Debunking The Paleo Diet.”

  46. On the quelling coughs subject: I have a long history of colds or flus turning into bronchitis which results in uncontrollable asthmatic coughing fits. This winter I got the flu for the first time in years and it was the only time I’ve been able to stop the coughing. I had one very small coughing fit after which I took 2000 mgs of buffered Vitamin C (mineral ascorbates from calcium and magnesium) every hour for 36 hours except when I was sleeping. I had absolutely no more coughing! As far as I’m concerned, this was a miracle. I’ve been dropped to the floor and almost unconscious from coughing, torn rib muscles and been seriously sleep-deprived before from these coughing fits. No doctor has been able to help me with this except for suggesting inhalers which I was not going to do unless absolutely necessary! This time it was simply not an issue. No sugar necessary. 🙂

  47. Natural cough remedy that could work is to have some ginger and lime/or lemon mix. I would add some honey, but it is your choice.

  48. For something truly paleo, just get some calamus root, or what the Cree call “rat root”. It looks like a small twig. Just bite off a small junk (in private; otherwise people will think you’re eating wood!) and either suck on it or chew it slowly. If it’s from a good batch, it will have a noticeable menthol flavour. It’s my absolute go-to remedy for a sore throat, but it may also work for coughs.

    I’ve never seen it in a health food store. I get it from a colleague who has connections to the local native community.

  49. Great advice on long haul flights. I used to travel 100,000 miles plus a year when I worked for the big corporates. I would add to avoid alcohol, drink lots of water to keep hydrated, and make a point point of several walks up and down the cabin to keep your muscles loose.

    Also put on the eye mask and if you have an ipod put on some soothing music at low volume, it cuts out all the plane noise and I find it helps a lot.

    I always set my watch to the destination time as soon as I get on the plane, mentally I am then working my sleep patterns around that.

  50. Mark, I’ve always looked for a way to be able to balance sleep when I travel. Whenever I traveled, I would be very sleepy at my destination and also when I return home. I’m going to give your tips a shot. It makes much more sense to do it that way.

    I ALWAYS take the window seat, I can’t stand passengers that have to get up to go to the bathroom every hour on the hour.

  51. Sucrets cough drops work. The ingredients are similar to halls with DM. The menthol starts working quickly and the DM affects something in your brain that makes you cough.
    I’d go for a natural remedy if I were you though.
    Small amounts of mint oil, like a droplet, have worked for me for soothing my throat and slightly opening my airways. Even sniffing or inhaling over the bottle works a bit.

  52. I’m APO E4/E4, and I get a bit frustrated at the conflicting recommendations. I recently read that carbohydrate sensitivity is common with E4s, and that is definitely my experience. Considering that Alzheimer’s disease is sometimes referred to as diabetes of the brain, I figure the best strategy is to eat in a manner that maintains endocrine serenity, which for me is avoiding starch and the huge spikes of blood sugar and insulin that starch creates. My diet is low-ish carb, with carbs from fruits and veggies making up about 25-30% of calories. Fat is about 50-60% of calories. Also, my evening meal is eaten at around 5pm, and it’s usually a small, easily digested snack of fruit or vegetables such that I sleep on an empty stomach and basically fast for ~12 hours every day.

    1. I think you are wise to control your carbs. I follow the research, and am e-3/e-4 and wrote a tome below if you are interested, I could have continued – but don’t want to be totally boring to all with my agenda, but I’ll weigh in on any specific questions you have as I do try to keep up with the literature and am personally very interested in the topic 🙂

  53. Research has found that Alzheimer’s patients have decreased insulin sensitivity in the brain and diabetes is a major risk factor for the development of Alzheimer’s Disease – hence regulating your insulin response should be beneficial as in a primal diet. The brain is the second major source in the body to make cholesterol, after the liver, it is essential to neuronal cell walls and functioning, and the e4 is less efficient and slower at transporting lipids/cholesterol than are the other alleles. Heavy metals do cause oxidative stress, and in my opinion, anyone who isn’t anemic, shouldn’t be taking iron in their vitamin supplements – you get what you need from diet and the body is very efficient at storing iron. In fact research has found that women that have early hysterectomies have earlier onset of dementia – possibly due to increased iron stores from not menstruating. On that note, estrogen is brain protective, we have estrogen receptors throughout the brain, and hormone replacement immediately following menopause likely decreases risk of dementia and slows aging (recent research from Standford shows preservation of telomere length with hormone replacement in e-4’s but rapid telomere aging without) – of course caution if one has significant cancer risk factors. A delay in hormone replacement will increase risk of heart disease and stroke if instituted later though. Nicotine is brain positive – just not when inhaled with the rest of the pollutants in tobacco. Exercise is the one variable that consistently has been shown to decrease risk of dementia, regardless of your apo e status. Blood pressure control is also very important – even longstanding borderline hypertension increases risk for dementia. Interestingly, the e-4 allele is more susceptible to herpes simplex type 1 (fever blisters) and some research suggests that HSV1 may cause chronic inflammation and be a co-factor in the development of AD – there is increased HSV1 viral DNA in AD brains (so maybe anti-virals are good – I take them 🙂 Also walking pneumonia, chlamydia pneumonia DNA is more common in the brains of AD patients, so chronic infection likely increases risk for AD. Some research shows e-4 brains to be different from birth, but the data on better memory doesn’t jive with the findings of smaller entorhinal cortices – so I don’t know about this discrepancy, but I do know of research that indicates higher IQ in e-4’s and some that doesn’t. I have read articles that showed that AD mice with a high fat, low carb diet have less Alzheimer’s pathology and better learning/memory, and the high carb diets having more Alzheimer’s pathology, but some of this research has been equivocal. I have also read research that reports lower incidence of Alzheimer’s Disease in hunter/gatherer societies, but longevity may have impacted the findings. On a discouraging note, I have also read an article that suggests that the e-4 is adaptive, would be genetically selected, in hunter/gatherers as around mid-age, one is not able to hunt or gather the calories needed to sustain oneself and as the brain is very caloric demanding, hence atrophy of “unneeded” functions can allow one to have preserved motor abilities and routine capacities, without the need for novel problem solving and memory, still contributing to the group and needing less resources for survival – bummer idea huh? I am an e-3/e-4 and a neuropsychologist who specializes in dementia. Unfortunitely my mother developed Alzheimer’s, which prompted my checking my own genetic status. On the positive, the e-4 is simply a risk factor, not a causal factor. Many people with e-2’s and double e-3’s also develop AD and many people with e-4 do not, so all you e-4’s don’t panic. I am primal because I believe it decreases my risk of manifesting Alzheimer’s Disease, based on the research, which I follow closely. Avoiding diabetes and insulin resistance is very important, controlling vascular risk factors, avoiding metals, pesticides, etc., and eating a diet high in anti-oxidants, healthy fats, and omega 3’s is important. Oh, and low levels of vitamin D are also associated with dementia – as well as many other things. Again, exercise – mental and physical – is preventative (not killer cardio – just regular exercise like walking), good social stimulation, good sleep, monitor your stress and cortisol (most of life is not so important as to stress about it), get therapy if you are depressed (depression is associated with earlier onset of dementia), avoid poisons, toxins, and excess metals, laugh, see the dentist regularly (poor oral health is associated with dementia), drink red wine and green tea, and eat dark chocolate (all decrease beta amyloid in the brain), take your omega 3’s and get sunshine or D3, and eat primal – and you may have a fighting chance, whether or not you are an e-4 carrier. Sorry this post is so long – there is so much to say about AD 🙂

  54. Excellent post, Nancy.

    AND, I appreciate Mark’s summary of the status quo regarding fats and APOE4. There are most definitely two schools of thought out there: the high fat camp vs. the low fat camp.

    One camp (Masterjohn) has taken it further and even suggested that a higher LDL-P is GOOD for E4’s- in the absence of inflammation.

    This is personal for me. I am the dreaded homozygous E4. With 25% of the population carrying at least one E4- that leaves millions of us without definitive dietary advice.

    This Primal follower, and millions of others, would greatly appreciate if you could look into this further, Mark. I am in touch with other homozygotes. We are desperately searching for research (and willing to participate in such!) that will give us an answer.

  55. The Berkeley Heart Lab offers a detailed and comprehensive panel of tests to assess the risk for cardiovascular disease for anyone interested.Genetic testing for ApoE as well as other genetic risk markers are included in the tests. Check it out! My physician is highly motivated to keep his patients stroke and heart disease free and he urged me to do it. The facts about Alzheimers disease became known to me after getting my lab results.

  56. Pretty tired of seeing the pseudo-science in disputing our meat-eating propensity with false-parallels.

    Yes, we don’t have claws, and large fangs. Big deal. When vegans can show me their four-chambered stomachs, hooves, regenerating incisors, or manufacture their own B12, then we can talk physiology as the salient justification for making a final decision.

    Until then, all we can do is try to make at least logical comparisons in order to find some sense of…well…sense.

    We’re primates. We have similar physical traits to other primates. Other primates spend a good deal of their effort obtaining vegetation, and unlike true herbivores, it tends to be high-quality vegetation utilized for nutritional value rather than simply packing on mass.

    Primates are generally opportunists that also eat insects and carrion. Essentially, our related physiology puts us not smack-dab as omnivores, but with a bias towards vegetation.

    Also, there are animals everywhere with claws that eat only vegetation (rodents, for example). Pandas have large canines, and they are pretty strictly herbivorous.

    No matter what, I concur that the WAY we treat other life that we consume as a commodity, as inferior, and horribly is extremely disgusting and disappointing, but beyond the ethical aspect, we’re made to consume animal matter, and that’s okay.