My Clementine

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In doing the background research on whether citrus increases the risk of melanoma enough to be a real concern, there was one more important study that was published this year. The same basic group of researchers who did the original examination of citrus intake in the two large healthcare professional studies added one more component. They used a database of FURs (furocoumarins) levels from 10 different foods that were included in the food frequency questionnaire and re-examined the data. This time, there was no relationship between FUR and melanoma; there was a small relationship with basal cell carcinoma but nothing of great significance.

I’m still going to eat my clementine every morning and drink my energy drink that has grapefruit juice in it when I want to. But these studies did raise at least two questions.

The Furocoumarins Database

The database was constructed by selecting foods that were suspected of having high FUR levels, which makes sense. The chemical analysis of each food is above my pay grade, but let’s assume it’s accurate since no one questioned it in the years since that study was completed. They purchased the foods for analysis from 17 different grocery stores in Connecticut and then analyzed three different samples of the same food purchased from different stores. All good.

The issue is that phytonutrient content can vary based on the season of the year, the ripeness of the fruit or vegetables, even the time of day it was harvested. FURs are stress-induced molecules. After harvesting, FUR levels can be affected by many factors ranging from ultraviolet light exposure to insect infestation. The levels can also vary by the variety of the fruit or vegetables. Then, when it comes to juice, there are processing and storage factors to consider. None of that was considered in the database study.

To be fair, buying foods that we actually eat is the right thing to do. But as a grocery shopper, you know that you can purchase two identical containers of food with two different expiration dates. That has to be accounted for, even if only to find out it doesn’t make a difference. In the case of FURs, it appears the date matters, based on prior research.

Food Frequency Questionnaires

If you’ve been reading the Memo for any length of time, you know that I’m not a big fan of food frequency questionnaires for the way they’re typically used today. The FFQ was designed to give an overall estimate of what people eat, but it’s not a measurement of what people actually ate. When you want to know the overall servings of citrus a person eats, fine. When you begin to break it down into extremely discrete serving portions, that’s where things fall apart in my opinion. Think of how many of these large studies that have used the FFQ that have gotten results that indicate nutrients are associated with some disease or another. In other studies, the reverse is true.

The reason that these are imprecise is because they were validated with a low number of subjects: 173 for one FFQ and 150 for another. The correlation coefficients are just not high enough to put a lot of faith in the FFQ for anything other than a general idea of diet. I’ve got a lot more to say about the topic but this isn’t the forum.

In addition, I think we’d be foolish to overlook the fact that the places where citrus grows in the backyard, and is therefore more convenient and available, are the same places that get more sunny days every year and more intense sun. The researchers controlled for self-reported sun exposure, but I’m almost as skeptical about that as about FFQs.

The Bottom Line

Based on the sum total of all the research, FURs are in some way related to the development of skin abnormalities, especially if you spend a lot of time in the sun. But given all the issues with the FFQ, at least in my opinion, it isn’t enough to avoid citrus if you typically eat or drink it. Pass my clementine, please.

What are you prepared to do today?

        Dr. Chet

References:
1. J Clin Oncol 2015:33:2500-2508.
2. Nutr Cancer. 2020;72(4):568-575.
3. J Food Science. 2011. doi.org/10.1111/j.1750-3841.2011.02147.x
4. J. Agric. Food Chem. 2017, 65, 24, 5049-5055.

Are Furocoumarins the Problem?

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If you’ve been reading the Memos for any length of time, you know I talk about phytonutrients a lot. They’re chemicals in plants that help the plant protect itself against threats such as bacteria, insects, birds, and anything that wants to eat them—such as humans. You might also believe that all phytonutrients are safe and beneficial. That might not be true. Let me explain.

The purpose of the studies on citrus consumption and skin cancer was related to the observation that a class of phytonutrients called furocoumarins (FUR) could be related to an increase in skin cancer, especially melanoma. It turns out that these phytonutrients are photosensitive; when exposed to light, they may cause damage to cell layers. Furocoumarins have been used as a treatment for psoriasis. And one of the major sources of FUR is citrus fruit.

In the study I mentioned Tuesday, the study found a 36% increase in cases of melanoma in those who consumed the most citrus, specifically grapefruit, compared to those who consumed the least. In a similar study on the subject in the Women’s Health Initiative, eating and drinking citrus resulted in a 12% increase in cases of melanoma over 15 years. That assumes that the fruit and juice actually contained the furocoumarins. More about that on Saturday.

What do the results mean for us? In 2016, 22 out of every 100,000 people had some form of melanoma. A 36% increase in the rate would mean that 30 out of every 100,000 people would be affected, and a 12% increase would be 26 out of every 100,000 people. Remember, that risk is for those who consumed citrus every day for 24 and 15 years respectively. As you might expect, nothing is as ever as simple as it seems as you’ll find out on Saturday.

What are you prepared to do today?

        Dr. Chet

References:
1. J Clin Oncol 2015:33:2500-2508.
2. Nutr Cancer. 2020;72(4):568-575.

Does Citrus Increase Melanoma?

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I could write about COVID-19 every week, but health is more than dealing with a viral pandemic, and it’s important we don’t neglect other aspects of our health while we try to keep ourselves safe. When the news and developments warrant, I’ll do an audio update so you can download it just like the free COVID-19 Bottom Line. But whenever we get to the new normal, we’ll still have some of the same health challenges; cardiovascular disease, diabetes, and cancer aren’t going away just because we have to self-isolate for a while.

A reader asked about a news article that showed eating and drinking citrus, specifically grapefruit, could increase the risk of getting melanoma, a severe form of skin cancer. A 2015 study based on the Healthcare Professionals Study and the Nurses Health Study showed a 36% increased risk of melanoma over 24 years when comparing those who consumed the most citrus with those who consumed very little. In doing the background research on the study, there were two other studies that demonstrated similar results.

Should we skip the glass of orange juice every day? What’s in citrus that could be a factor? I’ll answer those questions the rest of the week.

What are you prepared to do today?

        Dr. Chet

Reference: J Clin Oncol 33:2500-2508.

Natural ACE-Inhibitors

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Perhaps the thought crossed your mind that maybe you could get a prescription for an ACE-inhibitor. Maybe it was fleeting, just a wisp of a thought floating by, but it was there. Remember, a couple of studies do not a treatment make, and connecting dots doesn’t always end with the picture you think it might. We have no idea whether ACE-inhibitors will make any difference in dealing with the pneumonia from COVID-19.

Still, if there were something that we could do that might give us an edge from a natural source, wouldn’t that be a plus? It looks like some researchers have been examining that question for a long time; I read a review paper that provided some guidance.

Are ACE-Inhibitors Found in Nature?

Yes, is the short answer. The chemical structures of natural ACE-inhibitors vary, but they’re food peptides—short strings of amino acids, generally 2–50 amino acids long. When checking the BIOPEP Database, there were 891 peptide sequences that have been identified as having ACE-inhibitory traits.

The foods are diverse; they range from different types of fish such as sardines and Alaskan pollack, to chicken, eggs, beef, pork, and milk products. Vegetarian? No problem. Corn, wheat, soybeans, soy milk, garlic, chick peas, mushrooms, walnuts, and most likely, many more have the right properties.

Are All Natural ACE-inhibitors Biologically Active?

The ability of any peptide to work depends on its ability to survive the digestive system. Peptides can be broken down into their individual amino acids and may not reconstitute the sequence once absorbed. There’s limited research on extracts from foods and less on the foods themselves actually lowering BP.

We do have some research on whether a diet with these types of foods will lower hypertension; it’s called the DASH Diet. The foundation is whole grains, beans and legumes, lean proteins from meat, dairy, eggs, and fish. Together with reducing sodium and getting some exercise, the diet itself contains many naturally occurring ACE-inhibitory peptides. It may be that what lowers BP is the combined shift from a highly-processed, high-fat diet to the DASH Diet full of the right peptides.

The Bottom Line

Hypertension is one of the leading comorbidities for a severe case of COVID-19 if you get the virus. If you’ve been prescribed an ACE-inhibitor, I would recommend that you take it as directed. But it’s just as smart to add the foods with naturally occurring ACE-inhibitors in them. It may be that it’s what we’ve not been eating that’s putting us most at risk for a severe case of COVID-19.

What are you prepared to do today?

        Dr. Chet

Reference: doi: 10.1111/1541-4337.12051

Get This Free COVID-19 Audio

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The COVID-19 virus is impacting our lives, yet there seems to be a lot of confusion about what is and is not real. That’s why I’ve put together this free download on the COVID-19 virus. I’ve included the answers to questions I’ve gotten and divided them into a logical order. What is the history of the virus? Where did it come from? When will this be over? What do we do to protect ourselves? And finally, what are the myths surrounding the COVID-19?

This is the reference audio to use as baseline information. The numbers will certainly change; there will be new potential treatments; and there are certainly more myths being promoted every day. This audio is where to begin.

There are so many experts in all kinds of media right now, and you may wonder why you should listen to me. Here’s a link to my bio so you can see what my background is and decide for yourself.

What are you prepared to do today?

        Dr. Chet

What Is ACE?

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Angiotensin-converting enzyme—ACE—is the enzyme that converts angiotensin I into angiotensin II (ANG2). You’re probably thinking, “Well, that clears it up!” Here’s the problem: under the right conditions, ANG2 causes vasoconstriction and sodium and water retention, and the result can be hypertension because the overwhelmed kidneys can’t get rid of sodium or fluids.

However, it gets more complicated. There are two ANG2 receptors, A1 and A2, but A1 creates the problems related to blood pressure. It also contributes to pulmonary hypertension and pulmonary fibrosis under the right conditions. The problem is that we don’t know exactly what those conditions are.

What we are finding out is this: the lung contains A1 and A2 receptors, and it just so happens that the COVID-19 virus can use those receptors to allow the virus entry into cells. Once there, the viruses can multiply and may contribute to the extreme immune response of the lower lungs.

For people who are being treated for hypertension and are taking an ACE inhibitor, it would seem prudent to take your medication on schedule. If you take a medication whose name ends in “pril”—that’s your ACE inhibitor. We don’t know for sure that it will help and there’s a lot of research to go, but we will find out. Until then take your BP medications and do all those other things you’re supposed to do to lower BP.

What about the rest of us? Is there something we can do? Maybe and I’ll cover that on Saturday.

Reminder: my audio High Blood Pressure: Getting It Down is half price this week, CD or MP3. Learn more about what you can do to control your blood pressure.

What are you prepared to do today?

        Dr. Chet

References:
1. DOI: 10.1101/2020.02.24.20027268.
2. doi: https://doi.org/10.1101/2020.01.26.919985.

High Blood Pressure and COVID-19

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If you have hypertension, commonly called high blood pressure, and you’re taking a medication called an ACE inhibitor (angiotensin-converting enzyme inhibitor), make sure you take it regularly. It may—and I repeat, may—provide some protection against the COVID-19 virus. I’ll spend the rest of the week explaining why, but I want you to have that information first because you have no idea what you’ll be exposed to between now and Saturday.

What prompted this urgency? I read a Research Letter in JAMA Network that reported the comorbidities of people who died in 21 hospitals in Wuhan, China, between January 21 and 30, 2020; comorbidities are the simultaneous presence of two chronic diseases or conditions. The first indicator of morbidity (death) was age and try as we may, we can’t change that. The top modifiable morbidity was hypertension; half the people who died had high blood pressure. The second was diabetes.

Near the end of the short paper, the authors noted that hypertension is not a typical risk factor for sepsis, the uncontrolled immune-system response seen in the most serious cases of COVID-19. They commented that prior research had demonstrated that ACE receptors were discovered in the lungs; perhaps ACE inhibitors could be used as a potential treatment for the COVID-19 infection. More research is needed. I’ll examine this issue the rest of the week.

Insiders, remember there’s a Conference Call tomorrow night. I’ll explain this research and address some of the outlandish claims being made by so-called experts about cures for COVID-19 as well. If you’re not an Insider, go to the Store at drchet.com to check out how you can become one now.

What are you prepared to do today?

        Dr. Chet

Reference: JAMA Network Open. doi:10.1001/jamanetworkopen.2020.5619

Not So Smartphones

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Many variables that were included in the smartphone study weren’t reported, and there’s a good reason for that: they were non-significant. I don’t mean not statistically significant—I mean not significant in the real world either. In fact, I don’t think I’ve ever seen a study with so many variables that were non-significant.

The one that surprised me the most was that simple tracking of blood pressure or the use of the artificial intelligence (AI) application did not change the percentage of people who took their BP medications regularly. Neither approach shifted the scale one little bit. I would have expected that at least some people would have started taking their meds regularly, but they didn’t in either group. In next Tuesday’s Memo, I’m going to give you a good reason to take your meds based on a recent COVID-19 study.

Many of the variables were from questionnaires, and as I often remind you, self-reporting is always suspect. But it raised a few questions about the reported results.

Questions

The first question I had was related to the statistical analysis they ran. Instead of looking for differences within groups, they ran comparisons only between groups. I’m not saying that any differences were profound, but it did appear that there were some that were interesting.

For example, the control group demonstrated no differences in servings of processed meats per week, but the app group decreased servings by about one-half portion. The servings of sugar-sweetened beverages decreased by about a half-portion per week as well, while there were no changes in the control group. That would seem to be a benefit and if a statistical analysis were run, it might have been statistically significant—take a win wherever you can get it. You shouldn’t overstate the findings, but it does support the idea that reminders about a healthier diet might be effective.

I don’t understand why the researchers used an application that was being beta-tested for use in the study. If the number of subjects was limited, and AI requires a lot more data points to really “learn” enough to decide what the subjects need to know and how best to present it to them, it seems the study was destined to fail before it began. If they had called it a pilot study to gain insight to propose a major clinical trial, that would be more logical because that’s what pilot studies are for: to decide whether larger studies are warranted. They came to the same conclusion, but focused on what they didn’t show instead of what they did.

The Bottom Line

The use of smartphones, tablets, and laptops together with applications designed to monitor health are growing in use. Paula recently had a consultation with a specialist and her first telemed physical. I think there’s a place for these types of electronic services, especially during this unusual time. But no matter how many subjects are used to train AI, I think it will always stop short of what they hope applications will do, because there’s no app that will get people to do what they don’t want to do. No logic. No mini-goal setting. No reasoning.

I always thought that education was the key. It isn’t. Even with my education, I have trouble doing the things that I know I should do for my health. The willingness to change has to come from within. Until people have that, no program, person, or application will help them achieve their health goals. It’s wrapped up in the third word in my tagline: what are YOU prepared to do today? It is and always be your choice.

Because we’ve talked about blood pressure all week and more is coming next week, this seems like an obvious time to offer you my High Blood Pressure download at half price; only a few CDs are left, also half price, and when they’re gone, they’re gone. Members and Insiders who log in first will get their discounts as well.

What are you prepared to do today?

        Dr. Chet

References:
1. https://bit.ly/39OmUCc.
2. JAMA Open. doi:10.1001/jamanetworkopen.2020.0255.

Limitations of the Smartphone BP App

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In the examination of a smartphone application to help lower blood pressure, the results were a little surprising. Take a look at the graphic representation above of the study, including the results. More and more journals are going to that type of graphic summary. They’re great summaries, but they don’t always tell the entire story.

A quick review on blood pressure: systolic is the upper number and indicates the pressure when your heart is beating; diastolic is the lower number and indicates the pressure when your heart is resting. The ideal BP range is 110/70 to 120/80.

In this case, as you could see on the graphic, there was a difference of only 3 mmHg in systolic BP between those using the AI-generated coaching application and those who didn’t use that app. One of the discussion points was that the number of subjects was not great enough to be able to discern the significance of less than a 5 mmHg difference in BP. Achieving statistical significance is pretty much irrelevant in the real world if the difference between the approaches was so small. Yes, in a population of 50 million, a 1 mmHg drop in systolic BP may save some lives, but who do you really want tracking your BP: an artificial presence or your physician?

What really caught my attention was that both approaches worked. The overall decrease in the AI group was 8.3 mmHg versus 6.8 mmHg in the control group. There were decreases in diastolic BP as well. Whether it was the automated BP reporting alone or not, it appeared that just paying attention got results. But that’s not all I got out of the study. I’ll let you know more on Saturday. By the way, how you coming along with your new habit?

What are you prepared to do today?

        Dr. Chet

References:
1. https://bit.ly/39OmUCc.
2. JAMA Open. doi:10.1001/jamanetworkopen.2020.0255.

Get Health Support via Your Smartphone

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Paula has an appointment with her primary care doctor this morning, and she’ll be right here on the sofa when it happens. Telemedicine is now a part of everyday life, but your phone can be an asset to your health even beyond speaking to your doctor.

For example, hypertension is still a significant problem in the U.S., and it’s directly related to heart disease, stroke, and kidney disease. The typical treatments are medications, diet, and exercise. The problem is that too many people don’t follow through consistently enough to help themselves. Before I go any further, here’s a hypothetical: Imagine an application for your smartphone that would record your blood pressure and help you with diet and exercise recommendations and tracking; would that help you and others lower mild hypertension?

That’s what a group of physicians and public health officials in the Chicago area wondered. In the Smart Hypertension Control Study, they scanned more than 2,700 electronic medical records to find just over 300 people with mild hypertension to take part in a study comparing two different approaches to managing hypertension. Both the experimental group and the control groups used home blood pressure monitoring (HBPM) that could be reported automatically after it was taken with a Bluetooth connection to a smartphone. The experimental group used a smartphone app—a hypertension personal control program (HPCP).

The application used artificial intelligence to provide reminders and feedback along with diet and exercise information. The primary outcome was a difference in BP between the groups; I’ll tell you more about the results on Thursday. Until then, pick one single habit, such as taking your temperature or washing your hands, and through Saturday see how regularly you do that.

Hypertension is bad any time, but with a virus that seems to kill people with preexisting conditions, this is a great time to improve your habits.

What are you prepared to do today?

        Dr. Chet

Reference: JAMA Open.doi:10.1001/jamanetworkopen.2020.0255.