The Brain-Gut Two-Way Highway

This is Dr. Emeran Mayer. He has the rather niche dual specialty of being a gastroenterologist and a neurologist. He has published over 353 peer reviewed scientific articles, and he’s a professor in the Departments of Medicine, Physiology, and Psychiatry at UCLA. Much of his work has been pioneering medical research into gut-brain interactions.

We know the brain and gut are connected. What else does he want us to know?

First, that it is a two-way interaction. It’s about 90% “gut tells the brain things”, but it’s also 10% “brain tells the gut things”, and that 10% can make more like a 20% difference, if for example we look at the swing between “brain using that 10% communication to tell gut to do things worse” or “brain using that 10% communication to tell gut to do things better”, vs the midpoint null hypothesis of “what the gut would be doing with no direction from the brain”.

For example, if we are experiencing unmanaged chronic stress, that is going to tell our gut to do things that had an evolutionary advantage 20,000–200,000 years ago. Those things will not help us now. We do not need cortisol highs and adrenal dumping because we ate a piece of bread while stressed.

Read more (by Dr. Mayer): The Stress That Evolution Has Not Prepared Us For

With this in mind, if we want to look after our gut, then we can start before we even put anything in our mouths. Dr. Mayer recommends managing stress, anxiety, and depression from the head downwards as well as from the gut upwards.

Here’s what we at 10almonds have written previously on how to manage those things:

• No-Frills, Evidence-Based Mindfulness
• How To Set Anxiety Aside
• The Mental Health First-Aid You’ll Hopefully Never Need

Do eat for gut health! Yes, even if…

Unsurprisingly, Dr. Mayer advocates for a gut-friendly, anti-inflammatory diet. We’ve written about these things before:

• Making Friends With Your Gut (You Can Thank Us Later)
• Keep Inflammation At Bay

…but there’s just one problem:

For some people, such as with IBS, Crohn’s, and colitis, the Mediterranean diet that we (10almonds and Dr. Mayer) generally advocate for, is inaccessible. If you (if you have those conditions) eat as we describe, a combination of the fiber in many vegetables and the FODMAPs* in many fruits, will give you a very bad time indeed.

*Fermentable Oligo-, Di-, Monosaccharides And Polyols

Dr. Mayer has the answer to this riddle, and he’s not just guessing; he and his team did science to it. In a study with hundreds of participants, he measured what happened with adherence (or not) to the Mediterranean diet (or modified Mediterranean diet) (or not), in participants with IBS (or not).

The results and conclusions from that study included:

❝Among IBS participants, a higher consumption of fruits, vegetables, sugar, and butter was associated with a greater severity of IBS symptoms. Multivariate analysis identified several Mediterranean Diet foods to be associated with increased IBS symptoms.

A higher adherence to symptom-modified Mediterranean Diet was associated with a lower abundance of potentially harmful Faecalitalea, Streptococcus, and Intestinibacter, and higher abundance of potentially beneficial Holdemanella from the Firmicutes phylum.

A standard Mediterranean Diet was not associated with IBS symptom severity, although certain Mediterranean Diet foods were associated with increased IBS symptoms. Our study suggests that standard Mediterranean Diet may not be suitable for all patients with IBS and likely needs to be personalized in those with increased symptoms.❞

In graphical form:

And if you’d like to read more about this (along with more details on which specific foods to include or exclude to get these results), you can do so…

• The study itself (full article): The Association Between a Mediterranean Diet and Symptoms of Irritable Bowel Syndrome
• Dr. Mayer’s blog (lay explanation): The Benefits of a Modified Mediterranean Diet for Irritable Bowel Syndrome

Want to know more?

Dr. Mayer offers many resources, including a blog, books, recipes, podcasts, and even a YouTube channel:

The Hidden Complexities of Statins and Cardiovascular Disease (CVD)

This is Dr. Barbara Roberts. She’s a cardiologist and the Director of the Women’s Cardiac Center at one of the Brown University Medical School teaching hospitals. She’s an Associate Clinical Professor of Medicine and takes care of patients, teaches medical students, and does clinical research. She specializes in gender-specific aspects of heart disease, and in heart disease prevention.

We previously reviewed Dr. Barbara Roberts’ excellent book “The Truth About Statins: Risks and Alternatives to Cholesterol-Lowering Drugs”. It prompted some requests to do a main feature about Statins, so we’re doing it today. It’s under the auspices of “Expert Insights” as we’ll be drawing almost entirely from Dr. Roberts’ work.

So, what are the risks of statins?

According to Dr. Roberts, one of the biggest risks is not just drug side-effects or anything like that, but rather, what they simply won’t treat. This is because statins will lower LDL (bad) cholesterol levels, without necessarily treating the underlying cause.

Imagine you got Covid, and it’s one of the earlier strains that’s more likely deadly than “merely” debilitating.

You’re coughing and your throat feels like you gargled glass.

Your doctor gives you a miracle cough medicine that stops your coughing and makes your throat feel much better.

(Then a few weeks later, you die, because this did absolutely nothing for the underlying problem)

You see the problem?

Are there problematic side-effects too, though?

There can be. But of course, all drugs can have side effects! So that’s not necessarily news, but what’s relevant here is the kind of track these side-effects can lead one down.

For example, Dr. Roberts cites a case in which a woman’s LDL levels were high and she was prescribed simvastatin (Zocor), 20mg/day. Here’s what happened, in sequence:

1. She started getting panic attacks. So, her doctor prescribed her sertraline (Zoloft) (a very common SSRI antidepressant) and when that didn’t fix it, paroxetine (Paxil). This didn’t work either… because the problem was not actually her mental health. The panic attacks got worse…
2. Then, while exercising, she started noticing progressive arm and leg weakness. Her doctor finally took her off the simvastatin, and temporarily switched to ezetimibe (Zetia), a less powerful nonstatin drug that blocks cholesterol absorption, which change eased her arm and leg problem.
3. As the Zetia was a stopgap measure, the doctor put her on atorvastatin (Lipitor). Now she got episodes of severe chest pressure, and a skyrocketing heart rate. She also got tremors and lost her body temperature regulation.
4. So the doctor stopped the atorvastatin and tried rosovastatin (Crestor), on which she now suffered exhaustion (we’re not surprised, by this point) and muscle pains in her arms and chest.
5. So the doctor stopped the rosovastatin and tried lovastatin (Mevacor), and now she had the same symptoms as before, plus light-headedness.
6. So the doctor stopped the lovastatin and tried fluvastatin (Lescol). Same thing happened.
7. So he stopped the fluvastatin and tried pravastatin (Pravachol), without improvement.
8. So finally he took her off all these statins because the high LDL was less deleterious to her life than all these things.
9. She did her own research, and went back to the doctor to ask for cholestyramine (Questran), which is a bile acid sequestrent and nothing to do with statins. She also asked for a long-acting niacin. In high doses, niacin (one of the B-vitamins) raises HDL (good) cholesterol, lowers LDL, and lowers tryglycerides.
10. Her own non-statin self-prescription (with her doctor’s signature) worked, and she went back to her life, her work, and took up running.

Quite a treatment journey! Want to know more about the option that actually worked?

Read: Bile Acid Resins or Sequestrants

What are the gender differences you/she mentioned?

Actually mostly sex differences, since this appears to be hormonal (which means that if your hormones change, so will your risk). A lot of this is still pending more research—basically it’s a similar problem in heart disease to one we’ve previously talked about with regard to diabetes. Diabetes disproportionately affects black people, while diabetes research disproportionately focuses on white people.

In this case, most heart disease research has focused on men, with women often not merely going unresearched, but also often undiagnosed and untreated until it’s too late. And the treatments, if prescribed? Assumed to be the same as for men.

Dr. Roberts tells of how medicine is taught:

❝When I was in medical school, my professors took the “bikini approach” to women’s health: women’s health meant breasts and reproductive organs. Otherwise the prototypical patient was presented as a man.❞

There has been some research done with statins and women, though! Just, still not a lot. But we do know for example that some statins can be especially useful for treating women’s atherosclerosis—with a 50% success rate, rather than 31% for men.

For lowering LDL itself, however, it can work but is generally not so hot in women.

Fun fact:

In men:

• High total cholesterol
• High non-HDL cholesterol
• High LDL cholesterol
• Low HDL cholesterol

…are all significantly associated with an increased risk of death from CVD.

In women:

…levels of LDL cholesterol even more than 190 were associated with only a small, statistically insignificant increased risk of dying from CVD.

So…

The fact that women derive less benefit from a medicine that mainly lowers LDL cholesterol, may be because elevated LDL cholesterol is less harmful to women than it is to men.

And also: Treatment and Response to Statins: Gender-related Differences

And for that matter: Women Versus Men: Is There Equal Benefit and Safety from Statins?*

Definitely a case where Betteridge’s Law of Headlines applies!

What should women do to avoid dying of CVD, then?

First, quick reminder of our general disclaimer: we can’t give medical advice and nothing here comprises such. However… One particularly relevant thing we found illuminating in Dr. Roberts’ work was this observation:

The metabolic syndrome is diagnosed if you have three (or more) out of five of the following:

1. Abdominal obesity (waist >35″ if a woman or >40″ if a man)
2. Fasting blood sugars of 100mg/dl or more
3. Fasting triglycerides of 150mg/dl or more
4. Blood pressure of 130/85 or higher
5. HDL <50 if a woman or <40 if a man

And yet… because these things can be addressed with exercise and a healthy diet, which neither pharmaceutical companies nor insurance companies have a particular stake in, there’s a lot of focus instead on LDL levels (since there are a flock of statins that can be sold be lower them)… Which, Dr. Roberts says, is not nearly as critical for women.

So women end up getting prescribed statins that cause panic attacks and all those things we mentioned earlier… To lower our LDL, which isn’t nearly as big a factor as the other things.

In summary:

Statins do have their place, especially for men. They can, however, mask underlying problems that need treatment—which becomes counterproductive.

When it comes to women, statins are—in broad terms—statistically not as good. They are a little more likely to be helpful specifically in cases of atherosclerosis, whereby they have a 50/50 chance of helping.

For women in particular, it may be worthwhile looking into alternative non-statin drugs, and, for everyone: diet and exercise.

Further reading: How Can I Safely Come Off Statins?