Base AMA: Dr. Murdoc addresses our most popular questions on anxiety, caffeine, at-home testing and more.

Lola: Thank you for joining us in this Q&A session.

Today, I want to talk to you about the correlation between hormones, vitamins, nutrients and fatigue and anxiety, as well as other common questions that our community has for us.

During [2020 and] 2021, a lot of people got really anxious, and we discovered that sometimes quitting coffee helped that anxiety loop. There aren’t a lot of clinical trials to measure the effect of coffee and reported anxiety, but we published a story on our blog about Grace Clarke, who was super anxious at the time and had really high cortisol levels. You quickly pinpointed that could be due to coffee.

Can you tell us more about the correlation between anxiety, coffee, and hormones?

Dr. Murdoc: Coffee stimulates your hormones, and cortisol is our primary stress hormone. Caffeine can increase that stress hormone, which can then make us feel stressed or anxious.

[As humans,] we’ve evolved to have a stress response. Thousands of years ago, if an animal suddenly came upon us, and we needed to suddenly produce a lot of energy, our body would increase our blood flow to our muscles, and increase the blood sugar to provide energy---that was a good, healthy response. The problem is if we’re having that response all the time.

Various things can increase the hormone cortisol, such as not having enough sleep or being stressed, but also coffee. Coffee increases our blood pressure, blood sugar, and that’s why people drink it, to have that energy. The challenge is that that energy can also make them feel anxious, because of that elevation in the hormone cortisol, which is a stress hormone we can feel when it’s elevated and we can feel when we’re stressed.

When we look at Grace’s test results, her cortisol levels were sky-high. Nearly always, when I see cortisol levels that high, it’s often related to caffeine consumption because it’s not normal to have those high cortisol levels. We then discovered that she was consuming significant amounts of caffeine.

Lola:  As someone who likes to keep track of their hormone levels, I’ve noticed that during my PMS period, my cortisol levels are more elevated. So during that time, I usually only stick to one cup of coffee in the morning.

I’m definitely not representative of the majority of women since I am a founder of a company, and I work 12—14 hours a day, so I’m not sure if that’s a personal thing.

Have you seen that correlation between women’s biological cycles and their cortisol levels?

Dr. Murdoc: I can speak as an observer. I am not a woman, but I have been able to view thousands of biomarker patterns.

Observationally, during the premenstrual time, which is a more stressful time on the female physiology, the body can respond to that higher stress state with the stress hormone of cortisol. So you’re absolutely right, we sometimes see a pattern of an increase in cortisol during the PMS period.

Lola:  I cannot wait to continue to learn more about my levels and adjust my routines accordingly.

It’s such a life upgrade to be able to realize these things. In the past, I would be hyper-stressed during certain periods but was unable to pinpoint how to make it better because when you don’t know what’s really going on in your body or what’s causing things, it’s harder to fix it.

Lola: Switching gears a little bit, I want to talk to you about the Base test.

As you know, we partner with Quest Diagnostics for analyzing our tests. While they can still go to the lab, we do offer an at-home solution as a lot of people don’t want to go in, for various reasons---whether it’s inconvenient because they live far away, they’re busy, or they don’t want to get exposure to COVID.

A question we get a lot is, “Is this test accurate?” What’s your take?

Dr. Murdoc: There’s a reason why many people have skepticism about the test. They hear horror stories about companies like Theranos and they wonder if there’s a similar issue. What’s been interesting is that in response to the Theranos debacle, companies and laboratories have actually gone the extra mile to provide reassurance about the quality of their tests.

Beyond being just a CLIA-certified lab [meaning they meet the federal regulations for clinical diagnostic testing, ensuring quality and safety in the laboratory and laboratory results], some have gotten accredited by the College of American Pathologists (CAP).

CAP performs what’s called proficiency testing, which is essentially third-party validation testing. A  lab will perform tests on a sample, and this third party will also perform tests to see how closely they match to ensure the accuracy of the laboratory’s techniques.

Those two are the golden seals of approval for laboratories.

You’ve mentioned Base’s partnership with long-time established, large labs like Quest Diagnostics, who draw a fair amount of blood for the tests---which is the gold standard and considered to be 100% accurate.

Now, we also have more innovative techniques for at-home testing. While they’ll never be the gold standard (which is part of the reason why they have that third-party validation testing), the results are accurate enough that the decisions you make based on your results are the same.

There might be that small variation, say your result might be 4.09 instead of 4.1, but you still know if your results are low or high, or in the optimal range. What’s great about at-home tests is that you get the added value of that convenience of home testing while still having meaningful information to act accordingly.

Lola:  I’ve also worked in the lab industry creating lab testing technology, and I know that a traditional blood draw also has variations. You’d have the same machine running the same blood sample in different tubes, and you’d get some sort of variations as well in the results.

Sometimes, we have customers who wonder if the difference between our at-home test and their own test they’ve performed a month or two ago at a traditional lab is because of the fact that it was home testing.

How often do you see variation within levels? I’m not necessarily talking about something like HbA1c, which, from my understanding, takes about 3 months to meaningfully change, but something like cholesterol levels.

For example, if I were to go on a Keto diet or start taking some Vitamin D supplementation today, how would that affect the results? Something that we’ve noticed is that you could see a difference in cortisol if you take CBD really quickly, but what about other levels like cholesterol and vitamins?

Dr. Murdoc: I’m so glad you brought up the topic of variation because there are so many types.

As you’ve pointed out, in the actual analysis, when you use certain instruments in certain ways, variations will present themselves. You never get a precise number to the millionth of a percent, but you’ll get a result within some small range.

In addition, we all have physiological variations. We know, for example, that our blood sugar is different at one moment than it is at another. If you test it at two different times, you’re going to get two different measures for your blood sugar.

And that’s actually true for most biomarkers---the only difference is the degree of the variation and during what sort of time course. Something like Hemoglobin A1c (HbA1c), which you mentioned is your average blood sugar over the last four months, actually has a very tight variation. It takes months to change because it’s the average over months that collects sugar deposits on blood cells.

Other markers can change almost instantly. For example, different subtypes of cholesterol can literally change from laying down to standing. You can test in both and your cholesterol will be slightly different---not huge, not very significant, but there will be a slight difference. The same happens with your blood sugar if you suddenly move around a lot.

Then certain other markers are more in the middle. Say, if you start taking vitamin D, it will take a few days for it to increase your vitamin D levels. Or other types of hormones, like estrogen or testosterone, tend to operate on more of a days-to-weeks time course (obviously, with a woman’s cycle, they change throughout the month but as you make changes to your body, you build muscle or change your diet, they change as well). Yet they can also change suddenly, testosterone levels are much higher in the morning than they are in the evening.

Some of the markers you mentioned, usually vitamins, minerals, change within days of starting to take foods or supplements.

Lola:  Your answer brings me to the questions about the timing of testing, like collecting your test in certain circumstances such as being pregnant or being on birth control.

What happens if someone who is pregnant, potentially could get pregnant, or if they are on birth control and want to join Base to understand their fatigue or vitamin levels a little bit better?

Dr. Murdoc: That’s a great question because a lot of people ask whether or not their results are accurate if they’re pregnant.

The answer is, the results are accurate. If you test your cholesterol, estrogen, or anything else while you’re pregnant, the levels that you are getting are the levels you currently have.

I think the bigger question is, “Are they relevant if I’m testing during pregnancy?”

The answer to that is also yes, though there are some added challenges. When you’re not pregnant, there are very standard ranges for biomarkers---there’s a low level, there’s a high level for each biomarker, and you want to be within that range.

When you’re pregnant, you throw a lot of those ranges out the window. However, there are different normal ranges for someone who is pregnant. It is normal in pregnancy to have higher levels of cholesterol and blood sugar. It is normal in pregnancy to have estrogen and other hormone levels be very different from what they are when you’re not pregnant.

Testing during that period makes the markers a little harder to use, but not impossible. For example, cholesterol goes up during pregnancy, but if you test your cholesterol and they’re astronomically high, you can’t say that’s okay just because I’m pregnant. That will never be healthy.

Similarly, if other biomarkers are exceedingly abnormal, even past what one might expect due to pregnancy, then that is still an issue worth addressing. It will always be easiest to perform testing when not pregnant and you can have that tighter, more standardized range, but it’s still useful during pregnancy for specific things.

Lola: What about vitamins?

I have never been pregnant before, but I do know that Omega-3 supplements are quite popular. I wonder if people who are going through pregnancy should be focusing more on their energy levels than dietary-related ones.

Dr. Murdoc: I’m a big fan of testing vitamins and nutrients during pregnancy because the body demands so much more than usual.

I often hear people say, “What’s the point of testing these vitamins and minerals when we don’t typically see deficiency?” What they’re missing is that we often don’t see deficiency for the normal average human with the average diet.

Pregnant women have cravings because their body wants something in excess of what we normally consume with a regular diet. It requires higher levels of certain vitamins and minerals, and the easiest way to identify that is through testing.

I’d recommend testing things like folate, certain B vitamins like B12, and iron to make sure that the body’s increased demands are being met during pregnancy.

Lola: That makes so much sense.

Lola: Another question we get a lot as well is whether or not people should fast before collecting their samples, and what biomarkers are key to be measured while fasting versus which ones are okay to measure after having had a meal.

At Base, we have the melatonin and cortisol 3x, meaning we measure them throughout the day [for more accurate results as they fluctuate], but what about the other tests?

Dr. Murdoc: The answer is, sometimes. Fasting is helpful for specific tests. You want to fast for tests that are going to be strongly influenced by a meal, as it affects their predictive value.

Those are primarily two tests, and one is blood sugar.

Most research on prediction for diabetes risk and pre-diabetes, among other long-term health risks, has been performed on fasting blood sugar. Once you eat a meal, your blood sugar can skyrocket higher, and thus, that test is far less useful. There are certain types of tests for your blood sugar after you’ve had a meal but that’s not what’s commonly tested or as extensively researched.

The other that’s significantly impacted by what you eat before is the lipid panel, the various types of cholesterol like HDL cholesterol, LDL cholesterol, and especially triglycerides.

With the triglycerides test, the fats in the blood are tremendously impacted by a recent meal. Like blood sugar, there is a little bit of research on cholesterol after you’ve had a meal and its utility but that’s not what most research has been done, and that’s not where most risk ratification has been performed. To get the maximum value out of a lipid panel, you want to test it while in a fasted state.

Now, there are other markers that can be impacted by breaking a fast but that doesn’t really impact their utility. You gave the perfect example of cortisol, cortisol changes throughout the day, partly due to food. When you’re in a fasted state, cortisol levels are higher, and as you eat, cortisol levels come down.

Some people use only morning cortisol for a test, and there’s some utility there, but the greatest test is throughout the day, and seeing how that curve comes down---that will tell you a tremendous amount about your cortisol and overall stress state. We want to see how your cortisols evolve during your normal daily activities, so there’s no reason to fast for that test, even though it’s affected by eating.

So primarily, fasting is good for blood sugar, lipid panel tests. Nearly for all other tests, you do not need to fast for.

Lola: Adding to your comment about cortisol, we do see a lot of members that suddenly have spikes of cortisol in the evenings. You’ve mentioned before that cortisol blocks our primary sleep hormone, melatonin.

What’s the correlation between stress and sleep and how are those two key hormones affecting each other?

Dr. Murdoc: Those two are so intertwined that I often recommend getting both tested together. When one is not sleeping well, perhaps because their melatonin is off, you are going to wake up with elevated cortisol levels, and it is going to change your pattern throughout the day. And because of that stressed state you are in, you then may not sleep well the following night---and the cycle continues.

Not only does each affect the other, but both also have a natural physiological variation throughout the day. It’s somewhat opposing. Cortisol starts off at its highest and drops to its lowest levels in the evening when you go to bed. Melatonin is the opposite. Melatonin is at the lowest in the morning and increases until the evening and that’s what makes you sleepy.

If either of those is off, the other one is as well.

Lola: Have you ever seen Melatonin levels really high in the morning?

We’ve seen this happen with members who take a lot of supplementation. They start off with that problem of high cortisol levels in the evening, and then, they start over-supplementing to get it lower, and they get groggy in the morning when they wake up.

Dr. Murdoc: Not only have I seen that a fair number of times, but I’ve also experienced it as a physician who used to work a lot of night shifts. My circadian rhythms were heavily off, so I looked to correct that by taking melatonin.

It’s not necessarily wrong when one tries to correct those circadian shifts with melatonin, the challenge is that if the melatonin levels are too high, or if you take too high of an amount, you can fall asleep that night, but your normal physiological pattern is thrown off the following day. As you start off in the morning with higher levels of melatonin, you end up needing to continue to take them to fall asleep to restore a normal pattern.

There’s actually been research done on the optimal dosing of melatonin. To put this in context, most melatonin supplements are in the 5-to-10 milligram range, while the optimal dosing is considered about 200 to 300 micrograms. So most people are taking melatonin supplements that are 20 to 40 times what is optimal.

While it might help you fall asleep the night you’re taking melatonin, there are some long-term consequences. There’s a huge value to knowing where your pattern is to try and get away from that vicious cycle.

Lola: That’s super helpful to know, I’m going to retake my melatonin test after this conversation just to see where I’m at.

Thank you so much for joining us today.

Dr. Murdoc: Thank you for having me.

You can watch the whole AMA, here.