Dr. Lemanne
And then there's something that's really exciting, and my patients get really excited about this. And one of the things that melatonin does is that it modulates the effect of radiation. So it's both a radio-protectant, meaning if you're going to be exposed to radiation, you want to take melatonin ahead of time. And it also helps radiation therapy kill cancer cells. So that's the Holy Grail of cancer treatment, of course, is to kill the cancer cells while not killing or maybe even helping the non-cancer cells. And melatonin seems to do that. So there was a really interesting study. It was done in five healthy males between 25 and 35 years. And they were given a single dose of melatonin at 9:00 AM. And this dose was huge. It was 100 milligrams. 

 [00:01:17.850] - Dr. Gordon
I'm Dr. Deborah Gordon. I work with aging patients.

 [00:01:21.660] - Dr. Lemanne
We've been in practice a long time.

 [00:01:22.800] - Dr. Gordom
A very long time.

 [00:01:25.650] - Dr. Lemanne
We learn so much talking to each other.

 [00:01:27.400] - Dr. Gordon
We do. What if we How do people listen in?

 [00:01:34.850] - Dr. Lemanne
In this episode, Dr. Gordon and I discuss a common sleep supplement, melatonin. But we discuss its other powerful actions, such as its use as a pain reliever, an anti-anxiety medication, an antidepressant, and as a modulator of immune activity in autoimmune conditions. We also delve into melatonin's use in cancer, in particular in glioblastoma, where we look at a study showing a survival benefit to a particular melatonin protocol when combined with radiation. Our conversation also examines research suggesting that melatonin can be useful in providing protection from radiation damage, such as that that occurs during CT scans, X-rays, PET scans, and other high energy imaging studies. Then we discuss the controversy regarding the use of melatonin, especially in young people, and its dangers when used in the wrong setting. Dr. Gordon shares her artful use of melatonin in the aging population and how that differs from the way she uses it in younger people. Enjoy this wide-ranging conversation.

 [00:02:41.030] - Dr. Gordon
We didn't really come here to talk about the weather today, did we?

 [00:02:44.230] - Dr. Lemanne
I have something I'd like to talk about, Deborah.

 [00:02:46.800] - Dr. Gordon
Oh, good. What would that be?

 [00:02:48.600] - Dr. Lemanne
I would like to talk about melatonin and how I use it.

 [00:02:53.030] - Dr. Gordon
I would be very curious. I have some questions just that you say that, but I'm dying to hear what you're fascinated about melatonin today.

 [00:03:01.480] - Dr. Lemanne
Well, in oncology, melatonin is one of the... It's not one of the, it's the most studied supplement. And in oncology, most of the data in these studies is actually encouraging, meaning that melatonin seems to be helpful in oncology. But most people think about melatonin, they think about sleep, and it's a commonly used sleep supplement. People will buy it at their local drug store or their local grocery store or their local health food store and take it at night in hopes of getting a better night's sleep. But did you know that there are a lot of other uses for melatonin?

 [00:03:42.810] - Dr. Gordon
Well, I know there are a lot of other values to melatonin, but I think they mostly derived from part of its sleep-regulating mechanisms. What else would you say besides sleep? And how does--what does it do in cancer?

 [00:04:01.880] - Dr. Lemanne
Well, so some of the other things that melatonin does besides help some people get a better night's sleep, it actually can be used to treat anxiety. And so there have been studies looking at this, surgical anxiety, both before and after the operation, acute coronary syndrome, what we used to call heart attacks. Melatonin turns out not to be only better than a placebo. It turns out to be better than benzodiazapine.

 [00:04:34.300] - Dr. Gordon
Oh, and so much safer.

 [00:04:37.240] - Dr. Lemanne
When it's studied head-to-head with Alprazolam, oxazepam, these are, as you know, but for our audience, These are relative sister drugs in the Valium family, and they're powerful. So if you find something that's safer and works better for anxiety, that's a big deal.

 [00:04:56.910] - Dr. Gordon
That is a big deal. And I'm curious. So I track people's hormones that they secrete during sleep and pattern them.

 [00:05:06.250] - Dr. Lemanne
Tell me about that.

 [00:05:08.120] - Dr. Gordon
Let me ask my question first, and we can talk about that. Melatonin peaks at night and goes down in the morning when cortisol peaks. And they are thought of as complementary but balancing hormones. And that if I see somebody, it's almost uniformly true that—If  they complete for me the DUTCH test (the dried urine test for complete hormones). And I get back the results, as I did this week, where somebody's cortisol, particularly in the morning, is off the charts. They are showing up in their urine so many more cortisone and cortisol metabolites than you would normally expect to see when you thumb through a few pages later. It's really hard: Melatonin is secreted in the brain. I can't stick a needle into your brain and find out how much melatonin you're making. But your melatonin metabolites show up in the urine. And people with really high cortisol, almost uniformly, have really low subnormal levels, very wide range, but below that level of melatonin.

 [00:06:15.060] - Dr. Lemanne
So for our audience, cortisol, and correct me if I'm wrong, Dr. Gordon, but excess cortisol is a sign of stress?

 [00:06:23.070] - Dr. Gordon
Yes, or medication. It could be iatrogenic, of course, if you're on cortisone for because you have an acute flare of poison oak, you could be taking a form of cortisone or an autoimmune disease, something like that. But yes, and what's interesting is cortisol is secreted by the adrenal glands But clearly with some regulation from the brain and melatonin is secreted by the... Okay, how do you pronounce it?

 [00:06:53.310] - Dr. Lemanne
I say pineal.

 [00:06:54.330] - Dr. Gordon
I do, too. Some people say pineal gland, and I always want to correct.

 [00:06:59.910] - Dr. Lemanne
Are those East coasters?

 [00:07:02.870] - Dr. Gordon
No, I think they're the people who don't have MDs after their name, because in medical school, it was pretty uniformly pronounced pineal gland.

 [00:07:12.150] - Dr. Lemanne
Well, that is how I pronounce it. And So people who have... So you're saying that melatonin and cortisol, cortisol that's naturally made by the body, not taken by my mouth or some other way, are a seesaw. So one one's up, the other's down and vice versa. And you definitely see that when the cortisol is too high, then the melatonin is suppressed more than it should be. Is that what you're seeing?

 [00:07:40.910] - Dr. Gordon
Well, is it the other way around? Because what If you have too much cortisol, what is one of the adverse emotional symptoms you might have with that? Would be anxiety.

 [00:07:54.500] - Dr. Lemanne
Sure. And that may be how these studies worked, the mechanism behind Sure.

 [00:08:00.900] - Dr. Gordon
So it might be that those people start out not making enough melatonin and end up making more cortisol or because they're stressed for some other reason and make a lot of cortisol and end up suppressing their melatonin production.

 [00:08:13.540] - Dr. Lemanne
Sure. Exactly. So for instance, a stressful situation like surgery or a heart attack. Yeah.

 [00:08:19.890] - Dr. Gordon
Yeah. I think that- And so in those studies that you're talking about, these would be daytime uses of melatonin.

 [00:08:29.080] - Dr. Lemanne
I'll have go and look at the actual time of day that melatonin was given in these studies. That's a good question. And they don't know. But you raise a good point. What is the time of day that melatonin makes the There's a difference.

 [00:08:46.210] - Dr. Gordon
Yeah. And I would suggest that even giving it the night before, if you knew you were going to have surgery, would be helpful. But of course, you don't know the night before you're going to have a heart attack. Yeah, probably not. So I bet they give in the emergency room. Maybe. Maybe something like that. Yeah.

 [00:09:03.940] - Dr. Lemanne
We'll put the links to these studies in the show notes and people can look at those because I think if they're interested, because I think those are really interesting points. Yeah.

 [00:09:12.310] - Dr. Gordon
I've bumped up against... Well, I want to get to... I bump up against melatonin in a couple of other interesting settings recently. But you started at... You raised this question, so let's see where else you're going to run with it.

 [00:09:25.350] - Dr. Lemanne
So we have anxiety, and we have pain. So melatonin is a safe and effective treatment for all sorts of pain, even difficult to treat pain. So acute pain, chronic pain, even neuropathic pain, which every doctor knows is one of the most frustrating types of pain to try to help patients with. It doesn't respond to normal pain medications. The pain medication, the medications that will often help some people have tremendous side effects because basically neuropathic pain has to be quenched pharmacologically by quenching nerve transmission, signal transmission. And that is sedation, basically. The brain is a bunch of nerves. So if you start decreasing the transmission of nerve signals between the neurons in the brain, you get a lot of drowsiness, forgetfulness, falls. So there are a lot of problems treating neuropathic pain. So if we have something that is useful in that arena, we're very, very grateful to come across it. And it's something that's safe. And it's looking like melatonin, maybe that particular item that might help a lot of people with neuropathic pain.

 [00:10:47.530] - Dr. Gordon
That's an increasingly common problem as people get older. People have peripheral neuropathy, and it's whether from maybe diabetes, and I don't have that much diabetes in my practice, but sometimes it's from an injury proximal to the nerve, but sometimes it's from an imbalance of B vitamins, either too much or too little. And that peripheral neuropathic pain can drive a very sturdy person to their knees.

 [00:11:21.390] - Dr. Lemanne
Yes. So that was really of interest to me. Antidepressant activity. So melatonin, if you take it by mouth, it crosses blood-brain barrier. And we think that it's mechanism in depression is actually a soothing of brain inflammation is caused by free radical damage because melatonin is a powerful antioxidant, which makes it an anti-aging drug. So what do we have so far? We have anti-anxiety, we have an analgesic effect, we have antidepressants, we have antioxidants antiaging. And most of these seem to be related to melatonin's mitochondrial antioxidant effects. So melatonin is concentrated in the mitochondria of the cell more than in any other part of the cell.

 [00:12:18.150] - Dr. Gordon
When melatonin is in circulation near your cell, it goes via a cell receptor into the cell, meet the inside of the cell, but is active in the mitochondria?

 [00:12:32.770] - Dr. Lemanne
Yes, it seems to be collected by the mitochondria. And it certainly is made by the pineal gland. But it's also made in almost... It's found in every tissue. And in most tissues that have been looked at, There is an enzyme that actually produces melatonin. So we think that melatonin is produced in most tissues besides just in the pineal gland. So the pineal gland puts out a huge pulse of melatonin, which goes into the bloodstream and throughout the body. And that happens in the evening, and that sets the circadian rhythm. But there's also a lower amount of melatonin that is made in most tissues that the tissues use for themselves, possibly to protect mitochondria and other parts of the cell from free radical damage from oxygen metabolism. And of course, oxygen metabolism takes place in the mitochondria. So there's a lot of reactive oxygen species in the mitochondria to sop up by antioxidants. And that's one of the things that melatonin we think is very, very good at.

 [00:13:36.130] - Dr. Gordon
And is that particularly its usefulness in cancer? And when you said in cancer, are you talking about treatment, prevention, What's the angle? In a word? Yes.

 [00:13:51.450] - Dr. Lemanne
So there are a lot of studies looking at giving supplemental melatonin to cancer patients, particularly there's a lot of work in breast cancer cancer. And it does seem to have an additive effect along with the treatment for these cancers in that patients who take melatonin along with their treatment seem to do better than patients who just have the treatment without the melatonin. And And there is some actual hormonal effect of melatonin. We think that it calms and balances the estrogen-progesterone axis in especially postmenopausal of the women. We don't know how it does that, but that may be part of the mechanism, especially in breast cancer, that particular type of cancer.

 [00:14:37.280] - Dr. Gordon
I am writing that down because I have to look into that. In in my quest for isolating and separating the different kinds of estrogen receptors, which we've talked about before when we spoke about genestein, and that makes me wonder if melatonin, like Like Genestein and like hops, like other things, has a differential effect that helps estrogen be our friend and not so much our undoing.

 [00:15:13.160] - Dr. Lemanne
Yeah.

 [00:15:13.540] - Dr. Gordon
I have to look into that. It's a good thought.

 [00:15:15.980] - Dr. Lemanne
And then there's something that's really exciting. Okay. My patients get really excited about this. And one of the things that melatonin does is that it modulates the effect of radiation. So it's both a radio-protective, meaning if you're going to be exposed to radiation, you want to take melatonin ahead of time. And it also helps radiation therapy kill cancer cells. So that's the Holy Grail The cancer treatment, of course, is to kill the cancer cells while not killing or maybe even helping the non-cancer cells. And melatonin seems to do that. So there was a really interesting study. It was done in five healthy males between 25 and 35 years. And they were given a single dose of melatonin at 9:00 AM. And this dose was huge. It was 100 milligrams.

 [00:16:13.970] - Dr. Gordon
Oh, it is huge. Yeah. Yeah.

 [00:16:16.130] - Dr. Lemanne
And then they had some blood drawn. And then that blood was exposed to radiation. All right? The poor subjects weren't exposed to radiation, but their blood was. And then the blood cells were looked at for radiation damage, double-stranded DNA breaks. And if you're an oncologist, you double The term double-stranded DNA breaks sends a shiver up your spine because that is really difficult for cells to repair, and we think it leads to a lot of cancers. Basically, the bottom line is that melatonin ingestion before radiation caused a significant reduction in these double-stranded DNA breaks. And this effect was present both one hour and two hours after the exposure. And the dose, again, of melatonin, though, was large. It was 100 milligrams. But you know what's What's really interesting about melatonin is that there's no lethal dose has been found. So we don't see toxicity, even with huge doses of melatonin so far. It doesn't mean that there isn't any. I don't recommend that people go around taking huge doses of melatonin just to see if they can find some toxicity or something like that. That needs to be studied more. But in the large amounts of research that have been done, toxicity has not been Now, there are in terms of fatalities.

 [00:18:04.330] - Dr. Lemanne
That's not so with alcohol, for instance. I think one drink will not kill you, but 20 will. And one milligram of Melatonin will not kill you, and 20 milligrams won't, and 100 milligrams won't. So I have used this protocol for patients who are worried about radiation damage from, say, CT scans and PET scans and things like that. I'll have them take 100 milligrams of melatonin an hour before their scan. And there are some practical things that I think might be helpful to our listeners if they're thinking about discussing, perhaps using this protocol with their CT scan, and they're discussing it with their doctors first. Of course, they're not just doing it because I said so. They would not do that. None of our listeners will do that.

 (00:18:57.830] - Dr. Gordon
I don't believe you're our listeners' doctors, with a few exceptions. Right.

 [00:19:05.240] - Dr. Lemanne
So anybody listening to this who wants to do this, please discuss it with your doctor, because there are some drugs that can interact badly with melatonin, high blood pressure medications, certain blood thinners, things like that. So you definitely want to take a look at what you're doing with your doctor before you use There are high doses of melatonin. But I use 100 milligrams of melatonin. I have my patient take it one hour before. I like the liquid version for this because it's hard to gather enough pills, especially if you only have the three milligrams or the 0.3 milligrams or something like that at home. To get 100 milligram dose in all at once and taking a lot of pills is difficult. But there are liquid versions of melatonin which can get the job done very, very nicely. Again, patients should discuss this with their own doctors and make sure that there are no drugs or anything that they're on that might interact badly with this melatonin. These are blood thinners, antidepressants, blood pressure medications are some of those, not all of them.

 [00:20:14.840] - Dr. Gordon
Definitely not all of them because they've found a nice pairing. Patients who are put on beta-blockers, particularly metoprolol, which is a slightly longer lasting than the old-fashioned one, propranolol, It blocks your own melatonin production. And one of the side effects of metoprolol is difficulty sleeping. And they've done studies and paired those two categories of nighttime cocktails very beneficially. That melatonin blocks the insomnia effects of metoprolol.

[00:20:50.930] - Dr. Lemanne
I did not know that's so exciting. Dr. Gordon, that's so exciting. So you can fix the side effect of this particular very good A very good drug. Very good drug. By just adding a simple supplement.

 [00:21:04.660] - Dr. Gordon
And what would be interesting, I think still beta blockers, useful as they are, has the frequent side effect of fatigue on exertion. And I'm not sure using nocturnal melatonin helps diurnal fatigue on exertion, but maybe getting a better night's sleep would prepare you for a better day's exertion. I'm not on the medicine, but I have some I can ask about that. When you said radiation, it reminded me of something I read-I'm not just talking about radiation therapy, but imaging.

 [00:21:40.990] - Dr. Lemanne
So CT scans and X-rays and those kinds of things, protecting yourself from the radiation damage from a CT scan, which is a thing. There are statistics that tell us how much increased in risk of cancer there is with each CT scan, and patients Are they worried about that?

 [00:22:01.710] - Dr. Gordon
That reminds me of a patient I spoke to recently whom I wanted to go to the hospital for it was either a mammogram and or a bone density test, the most common two imaging tests I ordered. But she had had a number of X-rays recently staging her cancer. And she says, I just don't think I can take any more X-rays right now. And I could have said, well, you can wait a little bit. But even when you do, you could take 100 milligrams of melatonin and have somebody else drive you and you'd have some protection from that. Yes.

 [00:22:35.960] - Dr. Lemanne
And there are some other supplements that may be useful in that setting. What else? In that setting, for instance, high dose vitamin C, 2 grams. An herb botanical called gotu kola has some radio-protectant activity, and I believe ashwagandha may. None of these are foolproof. They don't necessarily remove every single risk, but they may help. And if that makes your patient feel more confident about the studies, it may be useful to her overall health.

 [00:23:05.560] - Dr. Gordon
It reminded me, and that's why I wondered, was talking about solar radiation, because as you just said, melatonin is in all the tissues. I was reminded of an awareness I had that melatonin is in skin tissues, and I was looking at it because it has some evidence or some reputation for slowing skin aging. So I can credit my meager assortment of wrinkles being so meager because I've been taking melatonin full disclosure, about 25 years. But it blocks some of the effect of UV radiation.

 [00:23:45.130] - Dr. Lemanne
Oh, very nice. Very nice. So, yes, the studies that I'm referencing are talking about nuclear radiation, high energy radiation, gamma rays, X-rays, those kinds of things. And UV radiation is, of course, a little bit lower energy than those. But that's very good to know.

 [00:23:59.960] - Dr. Gordon
Yeah. And I don't think it made me wonder, gee, they should put melatonin and sunscreen for people who've had solar radiation induced skin cancer, perhaps, something like that. That's a good idea. Good product line. Shall we set up a small- Topical melatonin. Small business.

 [00:24:20.210] - Dr. Lemanne
You might be out of something.

 [00:24:23.050] - Dr. Gordon
It's controversial for two reasons, and there's a lot more still to say about melatonin, but to acknowledge the fact that some of you have been told, Oh, you shouldn't take so much melatonin. Oh, you shouldn't take it all the time. And particularly a wonderful podcaster recently, Dr. Huberman. Alexander, is that his name?

 [00:24:46.040] - Dr. Lemanne
No, I don't think that's his first name.

 [00:24:48.200] - Dr. Gordon
Andrew. Andrew, beginning with an A. I think it's Andrew Huberman. Wonderful podcast. Always interesting. He has a little short YouTube video about why you should not take melatonin. Everything he says is 90% true for somebody under the age of 30. And that is a remarkable reality that's very well documented about melatonin, which is that your production of melatonin is huge. When you're from an infant to a teenager, it starts going down. And by the time you're 35, it's half of its peak. By By the time you're 45, you barely make any melatonin anymore. Of course, there are exceptions to the rule, but the tracing of melatonin level distribution, which peaks a couple of hours after you go to bed, is practically flat-lined past the age of 50. So the idea that I should not take melatonin is, I think, a misguided advice, whereas I would tell a 20-year-old, take melatonin a nights if you need it, but then stop because your own body has a rhythm to how the melatonin is pattered during the day that probably is smarter than I am and you are about when you should take melatonin.

 [00:26:11.360] - Dr. Lemanne
So certainly, I completely agree. And if you have a 20-year-old who has sleep issues, you certainly want to get to the bottom of it. It's probably not a deficiency of melatonin. Good point.

 [00:26:22.260] - Dr. Gordon
And you definitely want to find the most underlying reason that you can get to and try to I've got to address that if possible.

 [00:26:32.030] - Dr. Lemanne
But yes, when melatonin decreases with age, it decreases with Alzheimer's disease, with Parkinson's disease, it's definitely associated with aging. The pineal gland calcifies, which is where as we age, which is a sign that maybe things aren't working as well as they did when they were younger.

 [00:26:52.280] - Dr. Gordon
And that may be the cause of it, yeah. It's definitely a part of my protocol for almost all my brain patients because they're older and they have low melatonin. And there are some indication that particularly with early cognitive impairment, it helps. And partly it helps just because it helps them get night and day We sort it out and for some other benefits as well, as you said, the antioxidant ones. But it also has use in my recent passion, which has been bone health. Talk about that. So Melotonin has a role in bone injury of all sorts, whether it's arthritis, osteoporosis, a fracture, or something we talked about a couple of episodes ago, periodontitis affecting the bones of the mouth. So in the mouth, it has its antioxidant effect kicking in as well. But in the bones, what it does is you have stem cells in your bone marrow, and they can either, under duress, go, Oh, this is too much for me. I'm just going to become an inactive fat cell here in the marrow and not do anything. Or they can say, No, you know what? I think I'm going to take on the more noble job of trying to become a rigid bone cell or a trabecular bone cell.

 [00:28:21.950] - Dr. Gordon
And melatonin has a role in those stem cells making that distinction.

 [00:28:29.570] - Dr. Lemanne
So it sounds like their melatonin is preventing possibly a type of dormant state called senescence.

 [00:28:38.560] - Dr. Gordon
In the case of these cells in the bone. So we know sometimes senescence is useful, but we have too much senescence in aging bones, and we're going to try to get them to get off their butts and remember how to build bone the way they did when they were younger.

 [00:28:57.020] - Dr. Lemanne
Okay. That sounds wonderful. So I want to talk a little bit more about radiation. I think you had another question about radiation, and I was making a distinction between imaging radiation studies, CT scans and X-rays to look at parts of the body. And these are particular types of imaging. This is not MRI, which uses magnets, not nuclear radiation or X-rays to look at the inner structures of the body.

 [00:29:25.450] - Dr. Gordon
Nor is it an ultrasound.

 [00:29:26.700] - Dr. Lemanne
Nor is it an ultrasound. But nuclear studies such as PET scans, bone scans, and penetrating X-ray studies such as CT scans and X-rays, those are what we're talking about, but also radiation therapy. So There was a really nice study looking at glioblastoma, which showed that melatonin improved the cancer cell kill in patients having radiation to the brain while protecting the normal cells from radiation damage. And there was a survival advantage to the patients on melatonin compared to those not on melatonin. They used a pretty big dose. The dose there was 20 milligrams per day, which is a common dose in cancer studies and a common dose for cancer patients who want to use melatonin. A lot of them are using 20 milligrams per day. Again, before doing that, if you have cancer or you're worried about cancer, please discuss taking melatonin at those large doses with your It's our own doctor. Don't just do that because there may be interactions with other medications, et cetera. So it's not a treatment in itself for cancer, but it may help with radiation therapy, may help variation therapy work better, and may decrease the side effects from the radiation.

 [00:30:47.560] - Dr. Lemanne
So I think that's really interesting. There are not a lot of great treatments for glioblastoma, as you know. And so anything is welcome at this point.

 [00:30:56.040] - Dr. Gordon
So my understanding about radiation is scanty. That's a kind estimation of how well I understand it. It seems to me sometimes it's daily for two weeks and sometimes it's weekly for six weeks. And is that really right? Are the schedules all over the place? And how do you time the melatonin if you're having a patient who is undergoing radiation?

 [00:31:23.090] - Dr. Lemanne
Sure. So common radiation treatment patterns, it's a little bit different for each patient, but the radiation oncologist is the one who prescribes the radiation therapy and prescribes the dose and works out the correct dose. So for breast cancer treatment after lumpectomy, typically the treatment is five and a half weeks For five days a week for five and a half weeks, and there might be a little boost at the end for a couple of days or something like that. There is a similar schedule, five to six weeks for head and neck cancer with chemotherapy at the same time, similar for rectal cancer. So five to six weeks, five days a week is a really common schedule for radiation. And it's usually not given once a week or anything like that. That would be an unusual treatment. Sometimes for brain tumors, one or even two treatments, usually just one, are given. Really super high dose and super focused, called Gamma knife. There are some other names for that. So certain protocols can It could be for one day, but that's unusual. And you'd want to take the melatonin right before the treatment. So the study that we talked about before gave the melatonin an hour before the radiation was applied to the cells in that case.

 [00:32:44.300] - Dr. Lemanne
So I think that's a reasonable time frame. And so you want to have it next to the radiation treatment, just before the radiation treatment. Again, if you're using liquid, I would say make it an hour before, even a little bit less, because that's not going to take too long soak into your bloodstream and be at its maximum level. I wouldn't take it three minutes before. I don't think that's enough time. But I think 45 to 60 minutes before is a good time. If you're taking pills, for a lot of people, pills don't work instantly. It depends on your digestion. It can take pills 90 minutes or more to dissolve enough to release their contents into the digestive tract. And then from there, it still has to soak through the digestive tract walls and into the bloodstream. That process can take up to 90 minutes. So if you're going to take melatonin pills, I'd say take them 2 hours before you expect to be exposed to radiation.

 [00:33:41.440] - Dr. Gordon
And aside from its usefulness in optimizing radiation, optimizing the benefit, minimizing the side effects, do you see a use for melatonin in the other days, the other months and years of your treatment with cancer patients?

 [00:33:59.400] - Dr. Lemanne
Sure. With the studies that have been done, it certainly shows that there may be some significant benefit. The studies are pretty clear that there is some benefit. It's not miraculous, it's not huge, but there does seem to be some benefit in patients with cancer who take melatonin. So yes, and there's such a little small downside. I mean, again, for people who are taking certain drugs that may interact badly with melatonin, sure, that would be a reason not to take melatonin. But if they're not on those drugs and they don't have personally any bad responses, we'll talk a little bit about what kinds of bad reactions people might have to melatonin. But if they don't have any of those, there's very little downside, we think, to taking melatonin. And a lot of people take it very chronically. A lot of cancer patients take 20 milligrams per day, even 60 milligrams per day for long periods of time. Now, has that been studied? No. So there still ought to be some thinking about possible cautions that one could imagine with this. And again, it's something to discuss with your own health care team and your own doctors.

 [00:35:07.650] - Dr. Lemanne
But yes, a lot of cancer patients do seem to take a lot of melatonin and without any
apparent damage for most of them. So it's something to think about. And I think it's really interesting. It needs more study. And again, don't do this at home, not yourself. But do keep an eye on the news about this because I think it's It's something that may be very helpful for a lot of people.

 [00:35:32.950] - Dr. Gordon
And anybody who's taking medications or using it around the radiation, I think your caution about check with your doctor is wise. And I'm wondering, though, in general, for somebody over 40, if I just ran into somebody at the supermarket, I would say, Sure, take melatonin. It's safe. As you said, there's really no documented toxicity of it getting too high. But the other thing I say, whether I'm telling someone to take melatonin or vitamin C, is that any drug can cause any reaction. And if it does and you don't like it, you shouldn't take it.

 [00:36:20.200] - Dr. Lemanne
Yeah. Are you referencing the textbook of Common Sense?

 [00:36:26.020] - Dr. Gordon
Yeah. It's just what side effects What can I expect with this drug? Well, I'm not going to tell you that because that's-Oh, I will. No, for melatonin, I do want to hear it. But I mean, in general, if I'm giving someone a drug, I don't want to tell them the side effects. Oh, for the nocebo effect. I don't want them to be unduly influenced. And I do want them to report to me if their elbows turn green when that isn't an effect that I told them might happen with the medication. So I try not to prejudiced people, but I am curious.

 [00:36:58.300] - Dr. Lemanne
That does happen to me when my pens leak on my desk. You think it might be melatonin?

 [00:37:04.700] - Dr. Gordon
Either that or some plant-based herbal supplement that you're taking. I don't use those. That ashwagandha, which Why do you? I use a little bit and recommend it to my patients. Oh, that plant? Okay. Yeah. Oh, right. In Southern Oregon, we have to differentiate when we say plant, are we talking about vegans, cannabis, or just regular old plants, right?

 [00:37:27.780] - Dr. Lemanne
We're talking about plant medicine if we're in Ashtland, Oregon.

 [00:37:30.500] - Dr. Gordon
Yeah. So what do you think of as the common ill effects of melatonin?

 [00:37:36.670] - Dr. Lemanne
So people have reported depression, just feeling a little off the next day. And I wonder if that's the case, then I ask them to take melatonin a couple of hours before they want to go to bed, because I think it might just be that they haven't had enough time for the melatonin to wear off in the morning. So that's what I would try when somebody tells me that. But people can have really vivid dreams that are disturbing to them. Yes. Melatonin is closely related to a hallucinogen. Speaking of plant medicine, it's related to hallucinogen called DMT. And DMT is also produced by the pineal gland in very tiny amounts. It may play a role in rem sleep and dream production. We don't know. We don't understand that. Certainly, DMT is a drug used by injection and other ways for people who are trying to have a particular type of plant medicine experience. And so if If melatonin produces an unpleasant sensation in that realm, certainly stop. And those are the main things that people will report with melatonin. Vivid dreams that are unpleasant and depression.

 [00:38:47.210] - Dr. Gordon
Yes. And I would say the one you mentioned first, the hangover effect in the morning. And I have some patients who get a headache when they take melatonin. Okay. And I usually tell people who are my patients who I think should be on melatonin for one of the many reasons we're talking about here is to start with something like one milligram and work themselves up until they do feel like it might be too much and then back off. Because it's cumbersome to measure your melatonin in the urine to try and hazard a guess at what your melatonin is doing during the night. So I think subjective personal evaluation It suffices almost always unless I need to prove a point to somebody. See, you sleep really well, but you're making no melatonin. And we've just talked about how great it is for your immune system. Speaking of immune system- We didn't talk about that. Right, we didn't.

 [00:39:44.470] - Dr. Lemanne
Tell me about that.

 [00:39:46.090] - Dr. Gordon
Well, you might know in this slight little controversial pandemic we've just gone through and are still going through for these last three years, it was part of the early protocols and continued to be so, particularly for the people who were resisting conventional treatment or who would have relied on conventional treatment if they needed it but wanted to do as much as they could before they ended up with a serious disease or requiring hospitalization. That melatonin, 5 to 10 milligrams at night, was part of the alternative protocols. And at this point, I think, certainly in my practice, I keep alternative protocols like mouthwash. We talked about mouthwash when we talked about the microbiome.

 [00:40:40.380] - Dr. Lemanne
Sure.

 [00:40:40.800] - Dr. Gordon
And that I think of them as scorched earth chemicals that you only put in your mouth if you have something you want to scorch.

 [00:40:50.840] - Dr. Lemanne
You can have spicy food.

 [00:40:53.080] - Dr. Gordon
Well, I wouldn't. No. Yes, spicy food may serve just as well. But if I thought I just got exposed to COVID or was coming down with a flu, I might use mouthwash for a couple of days. I might take melatonin if I weren't otherwise. I might do a few things, but it's thought and has been included with a little bit more credibility than some of the alternative protocols that continue to be discounted time after time. Again, Ivermectin, I'm talking to you.

 [00:41:22.740] - Dr. Lemanne
Okay. So melatonin may be a little bit better than that.

 [00:41:28.280] - Dr. Gordon
Is that what you're saying? Yes. It has significantly observed immune modulating effects such that one of the things it does... So when you have an autoimmune disease, one of the hypotheses of the mechanism of action in your body is that you have an imbalance between the TH1 and the TH2 cells in your lymphocyte population. And it's usually that it's skewed one way or the other. You're stuck with way too many TH1 cells than TH2 or the other way around. It can be either way. And that can be part of the mechanism of an autoimmune disease and part of the rationale of some of the ways we try to work around resolving autoimmune disease. But melatonin can help rebalance the TH1, TH2, out-of-balance impaired immune system.

 [00:42:24.030] - Dr. Lemanne
A very interesting, very interesting. There are so many different doses. Should Can we talk about doses? How to use melatonin?

 [00:42:33.010] - Dr. Gordon
Yeah.

 [00:42:33.160] - Dr. Lemanne
So what I've learned from my reading is that for sleep, maybe the lowest dose is 0.1 milligrams, 0.3 milligrams may be best. And that if sleep is the issue, it's best to start low and then move up gradually if you need it. And so I wondered if you had any thoughts about that. And then And of course, for pain, there are different doses. We'll talk about that in a second. But sleep, what doses do you like?

 [00:43:06.420] - Dr. Gordon
So remember, I have a couple of patients under 50, but not many. So in my patient population, I usually have them start with three milligrams. And if they really know they have a bad history, I'll have them start with one milligram. But most people, a normal size adult 65-year-old walked in my office I'd say, start with three milligrams, increased three, six, nine, and end up with somewhere between five and 10. But one of the precautions I think is really important, and our favorite supplement reviewing company, Consumer Labs, was helpful in this. You go into the drug store. I don't advise that taking these because if you take those melatonins off the shelf, they have somewhere between 10 and 300% of the dose they say on the front.

 [00:43:59.110] - Dr. Lemanne
So the dosing information on the bottle may not be accurate?

 [00:44:04.700] - Dr. Gordon
Exactly.

 [00:44:05.480] - Dr. Lemanne
So people should look at Consumerlab.com and make sure that they're getting the best version of melatonin.

 [00:44:13.190] - Dr. Gordon
Yeah, get it How are you going to describe all of that story? We're a reputable company. So I think Source Natural is the most delving-into-sleep supplements of any other company just focusing on that. Life Extension is available. Everybody That's a good company. I have no investment in either one of these companies. And then some of the other high grade. And some of them you can get at a regular health food store. And yes, Consumer Labs is a great place for that. I love Consumer labs. So I start a little bit higher and have them again increase until they don't like it or just feel anything from it. And I tell them there's never really any need for my purposes of perhaps enhancing their long-lived health to go beyond 5 or 10 milligrams.

 [00:45:03.000] - Dr. Lemanne
So you're using it very artfully in that particular demographic. And if you were using it in a younger demographic, then you might start with a lower dose.

 [00:45:11.560] - Dr. Gordon
Lower dose and advise them to do it temporarily, because as you pointed out really wisely, a 30-year-old who has trouble sleeping and thinks they have a melatonin deficiency probably does not. They probably have something else going on.

 [00:45:25.110] - Dr. Lemanne
Right. And you want to address that. So it comes in different forms. So there's capsules, there's pills that are especially time-release pills. There's the oral liquid version that we talked about that I like to use for people who want to protect themselves from radiation. Then there are transdermal patches, rectal suppositors. There's all sorts of ways one can put melatonin into one's bloodstream. So there's a lot of options there. But for pain, I think it's really interesting. There's a study ongoing right now for pain, and it's We're studying 12 milligrams and giving it at night. And so that's the dose that is... That's the highest dose that's being given in this study. We'll see what the study ends up showing. This was just started in 2022, and I don't believe it's finished yet. But we'll put a link to the protocol in our show notes, and people can take a look at that study if they're interested. For radiation protection, again, we've talked about this a lot, but 100 milligrams, one or two hours before the imaging study or There are types of ionizing radiation. And then for cancer, somewhere between 20 and 60 milligrams per day is a commonly used dose.

 [00:46:39.370] - Dr. Lemanne
You'll know more about this than I do. But for neuroprotection, I read a study in Alzheimer's disease and Parkinson's disease, 40 to 100 milligrams per day.

 [00:46:51.490] - Dr. Gordon
In the study, I would not do... You can't do that in common practice with somebody. I have not seen that dose is used in clinical practice.

 [00:47:02.150] - Dr. Lemanne
Okay, so that's not something that's familiar in... In my world. In your world at this point.

 [00:47:07.690] - Dr. Gordon
You know, there is a side effect of melatonin, which I now remember circulating around with a group of my friends in the ancestral health community. Do you know a metabolic adverse effect that melatonin has?

 [00:47:24.390] - Dr. Lemanne
I can't. I can't say that I do. Enlighten me.

 [00:47:27.640] - Dr. Gordon
It boosts blood sugar, particularly morning blood sugar. It raises your fasting blood sugar. Interesting. And it can even contribute to a slightly higher hemoglobin A1c or overall average blood sugar. And the That is well countered. And what reminded me is that is well countered by what you suggested, the time release melatonin.

 [00:47:52.970] - Dr. Lemanne
Interesting. Okay. So if people find that it increases their morning blood sugar, they should go to the time released version?

 [00:47:58.570] - Dr. Gordon
Mm-hmm. That would minimize that effect of it. Yeah.

 00:48:03.490] - Dr. Lemanne
Interesting. Well, melatonin and insulin secretion are on a seesaw as well, correct? So if the melatonin shuts off insulin overnight, you might have a rise in your blood sugar. Is that the mechanism?

 [00:48:16.060] - Dr. Gordon
I don't think that's the mechanism. I think it has something to do with... We're going to look into it and clarify that. Is that what you know is that it...

 [00:48:29.090] - Dr. Lemanne
Melatonin and Insulin are antagonistic. So the reason you don't want to eat before you go to bed is because then you elaborate... Your pancreas elaborate insulin. Insulin suppresses melatonin secretion by the pineal gland. So you sit around all night with a high insulin level, which in oncology is of interest because insulin is a growth factor, drives the growth of many, many cancers. So I don't like my patients to have a late dinner and then go to bed because then insulin is around, their melatonin level is low because of the insulin. And they have a lot of signaling to their tumor to now is a good time to grow. Did you know that most cancers grow at night? No. I think that's why. Although there's a lot of work going on, and that's a really interesting new field. It was first discovered in breast cancer. Breast cancers grow and metastases at night. So you don't want to feed them right before you go to bed.

 [00:49:26.300] - Dr. Gordon
Well, and one of the important contributing risk factors to breast cancer, and I believe that's on the estrogen receptor positive, correct me, is nocturnal light exposure. Yeah. And I guess it's because it diminishes melatonin and there. Yeah. Okay.

 [00:49:45.570] - Dr. Lemanne
In some countries, if you work nights and you get breast cancer, you get a pension. It's considered an occupational disease. I think it's Denmark. If you're a flight attendant or a nurse and you get breast cancer, I think you get a medical leave pension.

 [00:49:59.810] - Dr. Gordon
And I think many nurses get a night differential for working nights as a contribution to the increased likelihood that they'll be getting something sick from it.

 [00:50:11.210] - Dr. Lemanne
Oh, is that worth it?

 [00:50:12.840] - Dr. Gordon
No, no, absolutely not. But some people really... I think I've shared with you a couple of my colleagues I respect the most in the world are night owls, and they are really night owls going to bed at dawn. So I don't think it's a good idea. And in the brain world, I don't like people to eat before they go to bed because not of the melatonin system, but because of the glymphatic system. The street-washing that your brain does every night, getting rid of the debris, doesn't perform as well if it's also dealing with incoming calories from a late night snack. So there are a lot of reasons not to eat. Everything is connected, isn't it? You shouldn't eat right before you go to bed.

 [00:50:56.810] - Dr. Lemanne
Yeah, everything is connected. Well, I don't want to end on that note about pensions and metastases. So melatonin is made by the pineal... Let's end here. Melatonin is made by the pineal gland, and it's made out of tryptophan, which is an amino acid. And so if you want to give your body what it needs to make melatonin, you would eat a lot of meat, poultry. You're going to love this list, Dr. Gordon. Meat, eggs, fish, shellfish. And then the last part, I'll just go through it quickly because you won't like it so much. Milk, legumes, nuts, seeds, and oats.

 [00:51:32.630] - Dr. Gordon
I do love oats. That's one of the grains I'm partial to.

 [00:51:36.730] - Dr. Lemanne
I like oats, but I don't always feel good after I eat them, so I don't eat them very much.

 [00:51:42.140] - Dr. Gordon
Do you eat rolled oats or still cut oats?

 00:51:43.760] - Dr. Lemanne
I cut my own oats in my... I have a little grinder, so I get whole oats, and right when I'm going to eat them, I cut them up myself.

 [00:51:50.480] - Dr. Gordon
And you harvest them out of the backfield before you do that? I grow them that morning. Okay, I'm coming over for an oat breakfast someday.

 [00:51:59.710] - Dr. Lemanne
We should have an oat supper because it always makes me sleepy. That's the problem with Oats.

 [00:52:02.770] - Dr. Gordon
That is definitely true. Oats make you sleepy.

 [00:52:04.790] - Dr. Lemanne
Maybe the tryptophan making melatonin.

 [00:52:07.270] - Dr. Gordon
Yeah, which is another good tip for extending your melatonin effect. When you take it by mouth, its primary effect is in the first couple hours. And that tryptophan you take with it has your body making more melatonin in the middle of the night.

 [00:52:19.670] - Dr. Lemanne
There you go. Great.

 [00:52:21.790] - Dr. Gordon
Well, a lot to go over, and I bet that we could have another episode about melatonin. Things are just popping up as you're speaking in in my search bar here. So there's more to talk about another time.

 [00:52:33.610] - Dr. Lemanne
Absolutely. I can't wait.

 [00:52:35.220] - Dr. Gordon
Good talking to you.

 [00:52:36.170] - Dr. Lemanne
Bye-bye. Bye.

 [00:52:39.240] - Dr. Gordon
You have been listening to the Lemanne Gordon podcast, where Docs Talk Shop.

 [00:52:45.010] - Dr. Lemanne
For podcast transcripts, episode notes and links, and more, please visit the podcast website at docstalkshop.

 [00:52:53.760] - Dr. Gordon
Com.

 [00:52:54.150] - Dr. Lemanne
Happy eavesdropping. Everything presented in this podcast is for educational and informational purposes only and should not be construed as medical advice. No doctor-patient relationship is established or implied. If you have a health or a medical concern, see a qualified professional promptly.

 [00:53:21.250] - Dr. Gordon
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 [00:53:33.340] - Dr. Lemanne
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 [00:53:47.770] - Dr. Gordon
Again, if you have any medical concerns, see your own provider or another qualified health professional promptly.

 [00:53:54.620] - Dr. Lemanne
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