Why the Blood-Brain Barrier Is So Critical (and How to Maintain It)

In-Line_Why_the_Blood_Brain_Barrier_Matters_11.01.16You all know about intestinal permeability, or “leaky gut.” The job of the gut lining is to be selectively permeable, allowing helpful things passage into the body and preventing harmful things from getting in. Nutrients get through, toxins and pathogens do not. Leaky gut describes the failure of this vetting process. But what about “leaky brain”?

A similarly dynamic barrier lies between the brain and the rest of the body: the blood-brain barrier. Since the brain is the seat of all the conscious machinations and subconscious processes that comprise human existence, anything attempting entry receives severe scrutiny. We want to admit glucose, amino acids, fat-soluble nutrients, and ketones. We want to reject toxins, pathogens, and errant immune cells. Think of the blood-brain barrier like the cordon of guards keeping the drunken rabble from spilling over into the VIP room in a nightclub.

The blood-brain barrier (or BBB) can get leaky, just like the gut lining. This is bad.

A compromised BBB has been implicated in many neurodegenerative diseases, like Alzheimer’s, Parkinson’s, and vascular dementia.

More generally, the BBB regulates passage of inflammatory cytokines into the brain, prevents fluctuations in serum composition from affecting brain levels, and protects against environmental toxins and infectious pathogens from reaching the brain. A leaky BBB means the floodgates are open for all manner of unpleasantries to enter the brain.

Some pathogens even wield chemical weaponry that blasts open the blood-brain barrier, giving them—and anything else in the vicinity—access to the brain. To prepare for that, you must support the integrity of your blood-brain barrier.


Optimize your B vitamin intake

In adults with normal B vitamin levels, mild cognitive impairment, high homocysteine levels, and a leaky BBB, taking vitamins B12, B6, and B9 (folate) restored the integrity of the blood-brain barrier.

Review this post and make sure you’re getting the B vitamins you need. Primal folks tend to overlook them.

Nourish your gut

A leaky gut accompanies, and maybe causes, a leaky brain. Funny how that works, eh?

It’s a rodent study, but it’s quite illustrative: a fecal transplant from healthy mice with pristine BBB integrity to unhealthy mice with leaky BBB and pathogen-filled guts restored the integrity of the blood-brain barrier.

DIY fecal transplants are an extreme intervention. Until that becomes more feasible, simply eating more prebiotic fiber, experimenting with resistant starch, taking a quality probiotic, and eating fermented foods on a regular basis will get you most of the way there.

Eat plenty of magnesium

Okay, Sisson. Enough already with the magnesium. We get it! But magnesium can attenuate BBB permeability, even if you inject an agent explicitly designed to induce leaky blood-brain barriers.

This is yet another reason to eat enough magnesium-rich foods (like spinach, almonds, blackstrap molasses, winter squash), drink magnesium-rich mineral water (I love Gerolsteiner, but you can also just go down to the local Euro food market and check the labels for high-Mg waters), or take a good magnesium supplement (anything ending in “-ate” like magnesium glycinate or citrate).

Don’t eat a 40% cocoa butter diet

Rodents given a 40% saturated fat (from cocoa butter) diet experienced elevated BBB permeability.

Except wait: The remaining 60% of calories was split up between white sugar, wheat starch, casein, and dextrin (PDF). So this isn’t the type of 40% SFA diet you folks are eating.

Except wait again: Adding in either aged garlic extract, alpha lipoic acid (ALA), niacin, or nicotinamide completely abolished the increase in permeability.

It looks like a refined diet high in saturated fat and sugar/starch and absent any phytonutrient-rich plant foods like garlic or antioxidant supplements like ALA will cause elevated BBB permeability (in rodents). I’m not sure I’d recommend a 40% SFA diet either way, however. Balance is probably better.

Use phytonutrient-rich plants and spices

Recall the study from the last section where some garlic extract was enough to eliminate the bad BBB effects of a refined lab diet. That’s because aged garlic extract is particularly rich in phytonutrients with strong antioxidant effects. What about other fruits, vegetables, and spices with different phytonutrients—do those also help BBB function?

Curcumin (from turmeric) certainly helps. Astragalus root, used in many ancient medical traditions, can help. Sulforaphane, from cruciferous veggies like broccoli, Brussels sprouts, and cabbage, shows promise.

Drink coffee and/or tea

As phytonutrient-rich plants, they technically belong in the previous section, but coffee and tea are so special that they deserve their own space. Both are sources of caffeine, a noted protector of BBB integrity.

Supplements can help

Supplement forms of the aforementioned nutrients are worth a look. Also:

Alpha-GPC (a type of choline that readily crosses the blood-brain barrier) has been shown to reduce BBB permeability in hypertensive rats.

Inositol (which you can get from foods like egg yolks but not in very large amounts) improves BBB integrity. Another option is to consume phytate-containing foods; if you’ve got the right gut bacteria, you can convert phytate into inositol.

Berberine, noted anti-diabetic compound, reduces BBB permeability and increases resistance to brain damage following head trauma.

Control your blood pressure

Both acute and chronic hypertension increase BBB permeability. This means you’ll have to control your sleep and stress. You’ll need to reduce insulin resistance. Eat dark chocolate (the horror). Figure out if you’re salt-sensitive (you may even have to increase salt intake if it’s too low). Get enough magnesium (yes, again) and potassium.


Sleep really is everything. You can’t avoid it, and if you skimp on it, things fall apart. The blood-brain barrier is no exception: sleep restriction impairs BBB function and increases permeability.

If you can’t stick to the bedtime you know is ideal, a little (0.25-0.5mg) melatonin can help set your circadian rhythm. Plus, supplementary melatonin may also preserve BBB integrity.

Don’t drink too much alcohol

Alcohol is a tough one. While I just wrote a big post explaining the merits of wine consumption, ethanol is undoubtedly a poison in high doses, and I derived real benefits when I gave it up for a few months. One way alcohol exerts its negative effects is by inducing BBB dysfunction. This allows both the pleasant effects of alcohol (low-dose ethanol migrating across the BBB and directly interacting with neurons, triggering endorphins and interacting with GABA receptors) and the negative effects (high-dose ethanol migrating across the BBB to damage the neurons, leaving the door open long enough for immune cells to sneak in and cause all sorts of trouble).

Stimulate your vagal nerve

After a traumatic brain injury or stroke, the resultant increase in BBB permeability floods the brain with inflammatory cytokines, causes swelling and neuronal death, and worsens the prognosis. Stimulating the vagal nerve after such an injury decreases the BBB permeability and improves the prognosis.

One treatment for epilepsy is to wear vagal nerve stimulators which send light electronic pulses to the nerve, akin to a pacemaker for the brain. Easier options include humming, cold water exposure (even just splashing the face can help), singing, chanting, meditating, deep breathing, coughing, moving your bowels (or summoning the same abdominal pressure required for said movement; girding your core for a heavy squat or deadlift should also work along the same lines), and many more.

Perhaps an entire post on the vagal nerve is in order. It’s an interesting area that impacts more than just the BBB.

Stop eating so often

Ghrelin is the hunger hormone. When you haven’t eaten in a while, ghrelin tells you that it’s time to eat. It also increases blood-brain barrier stability after (again) a traumatic brain injury.

So, never eat? No. But make sure to feel actual hunger. It’s the best spice, and it confers a whole host of other benefits, including better blood-brain barrier function. Heck, try intermittent fasting for the ultimate boost to ghrelin.

You might notice that a lot of the studies I cite involve traumatic brain injuries to rodents. Dropping a weight on a rat’s head or triggering a stroke in a mouse are two of the most reliable ways to induce BBB permeability. Brain injuries are also quite common in humans, and the BBB permeability that results is a major therapeutic target, but we can’t study it so easily in people. While acute and chronic BBB permeability are different beasts, and mice are not men, they operate along the same rough pathway.

That’s about it for today, folks. I hope you feel encouraged and able to fortify your blood-brain barrier. Don’t wait for cognitive decline to set in. Get started now.

How do you improve the integrity of your blood-brain barrier? Have you even considered it prior to today?

Thanks for reading!

Primal Kitchen Dijon Mustard

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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28 thoughts on “Why the Blood-Brain Barrier Is So Critical (and How to Maintain It)”

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  1. Another great article Mark thanks for your ongoing contribution to good health, don’t know how you come up with interesting and informative articles like this seven days a week!

    I have been studying health, nutrition and life extension supplementation for almost 40 years. I’ve been involved in n=1 biohacking for that length of time and constantly refining my approach. Those who wish to criticize and declare you can get all the nutrition you need from food are free to do so, and I respect that.

    Among the many supplements (and they should be “supplements” not a replacement for good nutrition) I take that are BBB related aside from B vitamins and fish oil are magnesium threonate, pyrroloquinoline quinone (PQQ), and curcumin as BCM-95. There are quite a few other supplements like astaxanthin etc. etc. that cross the BBB. I do eat all my meals within an 8 hour period (IF). I take probiotics and eat some fermented food along with a ton of veggies. Sleep … need to work on that!

    1. I would love to eat my meals within an 8 hour period…the only times I am successful with it are when I am getting more sleep. I’m curious about when you break your fast. If you drink coffee, do you have it black when you first get up? I can’t start the day without my crazy coconut oil/collagen coffee!

      1. Hey Elizabeth, yeah, your morning elixir is great, I’ve read about it on your blog! I drink a couple of glasses of tea that I brew up (green tea, oolong tea and tumeric) each day then once a day I have a protein drink with greens and in the evening I have a cup of lemon balm tea with collagen (you turned me on to the collagen, it’s really helped this old man’s skin LOL). Basically I eat my three meals between 11:30 AM and 7:30 PM to answer your inquiry (almost always slather some coconut oil on something). 🙂

      2. The 8 hour window is easy for me, but …
        I start the day with my coffee with butter (little slice), two spoonfuls of coconut oil and half a teaspoon (approx) of cream cheese).
        And on weekdays it is followed by a shot of brandy with lemon juice and a little of molasses for good measure (this is a recent addition)
        This is just before leaving for the workout in the park in the bike (on my way to work)
        And after my morning ritual of the foam roller pass.
        Am I cheating the 8 hours thing with this?

  2. Mark, your article is extremely timely. There is a little-known childhood illness called PANDAS/PANS that directly affects the blood-brain barrier. As many as 1 in 200 children are affected. My daughter has it and I have been hoping that the primal/paleo community would begin to talk in this area. A post regarding this autoimmune disease in children would be very welcome! Many parents use much of what you have listed in this post as home remedies to quell the flares. I can tell you that a bath in Epsom salt is a miracle during a flare!

    1. Hi. I don’t know if it might be useful, but have you checked thefamilythathealstogether? They have a child with the same illness as yours. They have a grain free /paleo viewpoint. I find many of their posts interesting.

  3. Always informative and eye-opening. If you had to order these in terms of most beneficial/impact, what would your top 5 be?

  4. Menopausal women no longer have the estrogen wrapper that allows glucose to pass through the BBB–this is why a keto diet is important after menopause. Without ketones, our brains “starve”, even though we may be swimming in sugar from the neck down (hence, T2 diabetes in middle age).

    Pseudo-estrogens (such as flax and soy) do nothing to help the glucose get to the brain.

    1. I would love to read source information for this. I’m really curious about it and would love to learn more about it!

    2. Do you have references for this info? Your brain uses a lot of energy. Either in the form of glucose or ketones. Most post menopausal women are not on a keto diet and one would imagine the brain would be dead within a day if what you are saying is correct.

  5. Eye opening post as usual. And no, I never gave the blood brain barrier any thought until right now. But all of the tips given are good for our overall health anyway, and thankfully I’m doing many of them already. I drink coffee and tea, use turmeric regularly, eat a diet high in phytonutrients, and magnesium is one of the few supplements I currently take. I don’t drink much alcohol, although I do enjoy some red wine from time to time, and I’m currently sampling a tasty beverage called COCO Cocktail (research for my blog!). I need to take a look at my B vitamin intake…really don’t know where I stand there. And sleep…my biggest issue. Quality is there, just need to work on quantity.

  6. No magnesium glycinate for me, hate the taste.
    Sticking with the citrate

  7. Thanks Mark, very interesting. I’m most interested in the intestinal permeability and brain permeability connection. Specifically, how some recommendations you make of moderate caffeine intake and Vitamin-B health (some B vitamins from nuts and eggs) can actually be disrupting to the gut and thus it seems the brain. Although I do understand some people’s guts to tolerate caffeine from coffee or tea, as well as others tolerating eggs, nightshades, and nuts. But it makes it so evident have personalized everyone is.

    Thanks again

  8. Mice are not men, indeed. For example, they don’t go around dropping weights on the heads of rodents. Wolves are not men, either. They eat the mice instead of just bopping them on the head. Now that, as we say, is Primal.

  9. I recently tested apoB and apo A1, however it was after 12 hours fasting. I see that fasting is not necessary, though, and non-fasting data is what is normally considered. So do you guys think my results are still valid or do I need to do it again? Thank you!

  10. I had a friend who died from complications of Alzheimer’s. He worked in the citrus industry in Florida. Citrus crops are often heavily sprayed with pesticides. I’ve always wondered if ongoing proximity to those poisons played a major role in the development of his illness. Another point worth considering: previously healthy people have come out surgery with full-blown Alzheimer’s, thanks to certain types of general anesthetics that were used. This info was courtesy of a relative who works in the medical profession but is also available online.

  11. Mark, what’s your two cents on transdermal magnesium? I take between 200-600 mg mag glyconate daily. I then add mag chloride via ‘magnesium oil’ to my shoulders and anywhere my muscles are tighter than usual. Anyone else use the mag oil or gel?

  12. Mark, now I have yet another reason to love my coffee so much. Thank you for that.

    Interesting in regards to alcohol and the brain. I am currently on a break from booze and have noticed some significant benefits. To this point, I would have described the benefits relating more to energy, but this has given me something else to think about.

  13. “Rodents given a 40% saturated fat (from cocoa butter) diet…”

    Oh-uh. That’s a bit troubling. Does evidence suggest the issue was cocoa butter specifically or saturated fat? My diet is made up of coconut oil and grass-fed butter so I would expect around 40% saturated fat.

    Hopefully it is just the cocoa butter and not sat fat in general…

  14. Take away: Follow a whole food diet and you won’t have to worry about this imaginary problem. File this worry under “needless”.

    I understand the interest in the subject from a purely intellectual point of view, but this is way off the radar for normal concern. Are we going to have “primal tips for watching TV” or “primal guide to fighting homegrown terrorism” soon?

    Again, love MDA, but my god, one needs to keep these “scare-of-the-day” posts in check or you’ll go insane.

    1. Sadly a reality for some of us living with a compromised BBB due to brain injury or medical intervention..So is hugely welcome sharing.

  15. Perhaps an entire post on the vagal nerve is in order. It’s an interesting area that impacts more than just the BBB.

    Yes please!

  16. I enjoyed the information, I have been Dx with m.s. 2010, been eating clean for quite some time, cognitive And balance Are big issues pt is helping but how can I get stronger with cognitive skills! I love spinach etc,green,reisha teas ….any input is appreciated, tia.