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Running on Empty: Your Brain's Power Stations and Depression - Wisdom Wednesdays · Hardiness with Dr Paul Taylor

• 0:04
  Speaker 1: Hey everyone, welcome to another edition of Wisdom Wednesdays. Now
• 0:08
  Speaker 1: today I want to talk about a widespread and increasing
• 0:12
  Speaker 1: problem and a really cool new way of looking at it.
• 0:15
  Speaker 1: Now that problem is depression and it's affecting more and
• 0:18
  Speaker 1: more people with the World Health Organization reporting that it
• 0:22
  Speaker 1: affects around 322 million people worldwide. Now, if you've ever
• 0:27
  Speaker 1: been properly depressed or you know someone who has, you'll
• 0:31
  Speaker 1: know that numbers like these don't really come close to
• 0:34
  Speaker 1: capturing what it feels like. One of the things that
• 0:37
  Speaker 1: people say most often about depression isn't actually, I feel sad.
• 0:43
  Speaker 1: It's more, I feel flat or I've got nothing in
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  Speaker 1: the tank. Everything feels hard, not because they don't care,
• 0:50
  Speaker 1: but because caring itself seems to cost more energy than
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  Speaker 1: they actually have. Now, for most of the last 50 years,
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  Speaker 1: we've explained that problem with chemistry, mainly the story about
• 1:02
  Speaker 1: serotonin and sometimes the other monomines. And that story has
• 1:06
  Speaker 1: been shown to be either incomplete or, in some cases,
• 1:09
  Speaker 1: just wrong. And today, I want to look at a
• 1:12
  Speaker 1: different take on the problem and one that's been gathering
• 1:16
  Speaker 1: evidence over the past decade or so. And it raises
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  Speaker 1: a simple question. What if, for at least some people,
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  Speaker 1: Depression is partly a problem of energy supply inside the
• 1:27
  Speaker 1: brain cells in the tiny structures called mitochondria. Now that
• 1:32
  Speaker 1: is the argument of a 2024 review by Jiang Wang
• 1:37
  Speaker 1: and Sheng published in CNS Neuroscience and Therapeutics Journal. And
• 1:42
  Speaker 1: at the end of this episode, I'm also going to
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  Speaker 1: tell you what I do each week to look after
• 1:47
  Speaker 1: my mitochondria. some of which is really solid evidence-based and
• 1:51
  Speaker 1: some of which I am definitely hedging my bets on. Now,
• 1:55
  Speaker 1: let's talk about the mechanism first. You probably remember from
• 2:00
  Speaker 1: school biology that mitochondria are the powerhouses of the cell,
• 2:05
  Speaker 1: but that is definitely not all that they do. Now,
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  Speaker 1: every thought that you have, every flicker of motivation and
• 2:13
  Speaker 1: every time you manage to resist sticking your hand in
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  Speaker 1: the cookie jar, that runs on a molecule called ATP,
• 2:21
  Speaker 1: the energy currency that your cells spend just to exist. Now,
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  Speaker 1: your mitochondria take fuel from your food, mostly glucose in
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  Speaker 1: the brain's case, and they convert it into ATP. And
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  Speaker 1: the final stage of that process is called the electron
• 2:38
  Speaker 1: transport chain, which you may remember from high school biology. Now,
• 2:43
  Speaker 1: The electron transport chain is a series of four protein
• 2:47
  Speaker 1: complexes embedded in the inner membrane of each mitochondria. And
• 2:52
  Speaker 1: it's important that we understand it. So electrons get stripped
• 2:56
  Speaker 1: from your food and they are passed from one complex
• 2:59
  Speaker 1: to the next. And each step pumps protons across that
• 3:03
  Speaker 1: membrane building up a gradient. Now at the end of
• 3:07
  Speaker 1: the chain, oxygen accepts the electrons and the protons flow
• 3:12
  Speaker 1: back through a fifth complex called ATP synthase, which uses
• 3:17
  Speaker 1: that flow to make ATP. Now later in the episode,
• 3:21
  Speaker 1: I'll go through the chain complex by complex and tell
• 3:24
  Speaker 1: you which nutrients each one depends on because it is
• 3:27
  Speaker 1: really important. Now, this is important for your mood because
• 3:31
  Speaker 1: your brain is around 2% of your body weight, but
• 3:35
  Speaker 1: uses something like a fifth or 20% of your energy
• 3:39
  Speaker 1: at rest. And that increases as you use a lot
• 3:43
  Speaker 1: of cognitive load. And unlike your muscles in your liver,
• 3:47
  Speaker 1: it can store almost no fuel. Now, this review that
• 3:51
  Speaker 1: I'm talking about points out that glucose metabolism supplies more
• 3:55
  Speaker 1: than 95% of the brain's ATP. So the brain depends
• 4:00
  Speaker 1: on minute by minute supply. And when that supply falters
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  Speaker 1: even slightly, it's among the first organs to feel it. Now, mitochondria,
• 4:09
  Speaker 1: they're not fixed in one place. They're constantly being built, repaired, merged,
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  Speaker 1: split apart. And when they're beyond saving, the body actually
• 4:18
  Speaker 1: breaks them down and recycles them. And it's really cool.
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  Speaker 1: And researchers call this the mitochondrial quality control system. And
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  Speaker 1: it's got four main processes, which we need to understand.
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  Speaker 1: So the first is biogenesis, and that is the building
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  Speaker 1: of new mitochondria. Then we have fusion, which merges healthy
• 4:40
  Speaker 1: ones together so as they can share resources. And then
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  Speaker 1: you have fission, which splits off damaged sections of mitochondria.
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  Speaker 1: And then we have this really important thing called mitophagy,
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  Speaker 1: which literally means mitochondrial eating. And that removes the ones
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  Speaker 1: that are past repair and actually recycles them, which is
• 5:01
  Speaker 1: a pretty cool process. Our body is an amazing recycling machine. Now,
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  Speaker 1: when any of these fall behind, the cells end up
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  Speaker 1: full of worn, inefficient mitochondria that produce less energy and
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  Speaker 1: they produce more oxidative damage. And that causes inflammation and
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  Speaker 1: this has a direct impact on our energy levels. And
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  Speaker 1: mitochondrial dysfunction occurs is one of the 12 recognized hallmarks
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  Speaker 1: of aging that I've talked about before. And I've mentioned
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  Speaker 1: before that I think it is the most important of
• 5:34
  Speaker 1: the 12 hallmarks of aging. Okay, so that's the background.
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  Speaker 1: Let's talk about this study. So this review comes from
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  Speaker 1: a physiology group at the Naval Medicine University in Shanghai,
• 5:46
  Speaker 1: and they put together 105 different research papers that covered
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  Speaker 1: human patients, analysis of post-mortem brains, cell cultures, and a
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  Speaker 1: whole heap of animal studies. Now their starting point is
• 6:00
  Speaker 1: that more than a third of people with depression don't
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  Speaker 1: respond adequately to antidepressants we currently have. So our current
• 6:07
  Speaker 1: model of depression is clearly incomplete. Now the first line
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  Speaker 1: of evidence concerns the structure of mitochondria. In a standard
• 6:16
  Speaker 1: lab model called Chronic Unpredictable Mild Stress, Rodents are exposed
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  Speaker 1: to weeks of small random hassles. And it's kind of
• 6:25
  Speaker 1: the rodent equivalent of us having a shit month. And
• 6:29
  Speaker 1: the mitochondria in their hippocampus end up swollen with their
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  Speaker 1: internal folds in the mitochondria broken down. Now these folds
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  Speaker 1: called cristae are where the electron transport chain sits that
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  Speaker 1: I talked about earlier. So damage there directly limits energy production.
• 6:48
  Speaker 1: And one of the author's own earlier studies found that
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  Speaker 1: treadmill exercise repaired some of this damage in rats exposed
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  Speaker 1: to stress hormones before birth, which is worth remembering for
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  Speaker 1: later on. Now, the second line of evidence is about
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  Speaker 1: energy output. Brain imaging studies in people with major depression
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  Speaker 1: show lower glucose metabolisms in regions involved in regulating emotion,
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  Speaker 1: including the insula and the cingulate cortex. And spectroscopy studies
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  Speaker 1: have found lower levels of ATP-related molecules in the basal
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  Speaker 1: ganglia in the brain. And in mice, chronic social stress
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  Speaker 1: drains ATP from parts of the brain. And in a
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  Speaker 1: study published in Nature Medicine, topping up ATP either by
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  Speaker 1: injecting it directly or promoting the brain's support cells to
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  Speaker 1: release more of their own reversed the depressive-like behaviour. And
• 7:44
  Speaker 1: post-mortem studies have also found reduced levels of components of
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  Speaker 1: complex 1, the first complex in the electron transport chain,
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  Speaker 1: in people who had major depression. Then the third line
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  Speaker 1: of evidence involves lactate. So when mitochondria can't keep up
• 8:00
  Speaker 1: with demand, cells fall back on a faster but less
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  Speaker 1: efficient way of burning glucose that doesn't need box oxygen
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  Speaker 1: and produces lactate as a byproduct. So this is anaerobic metabolism.
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  Speaker 1: Several studies have found raised lactate in the brains and
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  Speaker 1: cerebrospinal fluid of people with depression. And one even found
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  Speaker 1: that higher lactate in a region called the pregenual anterior
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  Speaker 1: cingulate cortex tracked with more severe symptoms. Now, lactate on
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  Speaker 1: its own doesn't tell you what the problem is, but
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  Speaker 1: it's a reasonable sign that the mitochondria aren't meeting the
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  Speaker 1: demands and that the brain reverts to plan B for
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  Speaker 1: energy production. And then the fourth line of evidence concerns
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  Speaker 1: the quality control system. So PGC1-alpha, which is a hugely
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  Speaker 1: important protein that switches on the building of new mitochondria,
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  Speaker 1: has been found at lower levels in the blood of
• 9:00
  Speaker 1: people with depression and in the brains of chronically stressed rodents.
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  Speaker 1: And markers of mitophagy, which remember is the cleanup process
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  Speaker 1: in the mitochondria, also appear sluggish in depressed patients' blood cells,
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  Speaker 1: and in stressed mice the recycling process seems to stall altogether.
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  Speaker 1: In several animal studies, restoring that recycling improved the animal's
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  Speaker 1: behaviour and outcomes. Finally, the authors make an interesting observation
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  Speaker 1: about the drugs that we generally use already. Antidepressants were
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  Speaker 1: never designed with a mitochondrion mind, yet in animal studies,
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  Speaker 1: several antidepressant drugs appear to increase activity in the electron
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  Speaker 1: transport chain or support the quality control system, and that
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  Speaker 1: may be part of the mechanism by which they work
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  Speaker 1: whenever they do work. Now, ketamine, which is a fast
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  Speaker 1: acting treatment used for treatment resistant depression appears to restart
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  Speaker 1: mitochondrial recycling in the prefrontal cortex of mice and in
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  Speaker 1: one human study mitofusion 2 which is a protein involved
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  Speaker 1: in mitochondrial fusion was markedly reduced in vesicles shared from
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  Speaker 1: the neurons of depressed people and treatment with antidepressants brought
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  Speaker 1: it back up So it's possible, though not proven, that
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  Speaker 1: part of the reason that the existing medications work when
• 10:24
  Speaker 1: they are effective is that they improve mitochondrial function. Now,
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  Speaker 1: before we rush off and start buying any supplement that
• 10:33
  Speaker 1: has METO on the label, it's worth being clear about
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  Speaker 1: the limitations of this paper. Now, most of the evidence
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  Speaker 1: comes from stress rats and mice. And a mouse that
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  Speaker 1: stops preferring sugar water is telling us something about stress biology.
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  Speaker 1: But it's a long way from a person lying awake
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  Speaker 1: in three in the morning and going through rumination, right?
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  Speaker 1: So the human evidence comes mostly from blood cells, brain scans,
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  Speaker 1: and post-mortem tissue, which shows us that mitochondrial changes travel
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  Speaker 1: alongside depression. But as you'll know, it always doesn't mean
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  Speaker 1: that it is a cause, right? So correlation is not
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  Speaker 1: always causation, right? And that does raise the question of
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  Speaker 1: cause and effect. If you're depressed, you move less, you
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  Speaker 1: sleep worse, you often eat worse and you spend more
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  Speaker 1: time with elevated stress hormones and each of those on
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  Speaker 1: its own will degrade your mitochondria. So lower brain energy
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  Speaker 1: could be a cause of depression, it could be a
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  Speaker 1: consequent of it or most likely in my view, it's
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  Speaker 1: part of a cycle in which each makes the other worse. Now,
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  Speaker 1: the authors of this study also pointed out that the
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  Speaker 1: findings from different studies don't always agree, which is pretty
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  Speaker 1: common in research. One fusion protein goes down in one
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  Speaker 1: group of patients and up in another. One energy-sensing protein
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  Speaker 1: appears protective in one brain region and harmful in another.
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  Speaker 1: And in a test tube study of brain tissue of pigs,
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  Speaker 1: several neuro-antipsychotic and antidepressant drugs actually reduced mitochondrial ATP production,
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  Speaker 1: although they were used at very high concentrations, right? Now,
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  Speaker 1: and this is a narrative review rather than a systematic review.
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  Speaker 1: So the authors choose which studies to include. They didn't
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  Speaker 1: look at pooled effect sizes and a formal assessment of
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  Speaker 1: study quality, right? So it's a theoretical paper, but it
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  Speaker 1: is becoming increasingly clear that depression is not one disease
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  Speaker 1: with one cause and nobody should really be thinking because
• 12:43
  Speaker 1: of this paper that it's just a mitochondrial problem or
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  Speaker 1: that a supplement can replace treatment. So if you're struggling,
• 12:50
  Speaker 1: please talk to your GP or psychologist. And if your medication,
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  Speaker 1: this is certainly not a reason for changing your medication.
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  Speaker 1: What this is about is a plausible biological reason why
• 13:03
  Speaker 1: the things that keep your energy systems healthy might also
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  Speaker 1: keep your mood resilient. And that's the basis of my
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  Speaker 1: own routine. So let's talk about the stuff that I do.
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  Speaker 1: What I do for my mitochondria is three different parts.
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  Speaker 1: Because I am convinced about the role of mitochondria in
• 13:24
  Speaker 1: healthy aging and especially in brain health. So the first
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  Speaker 1: part is exercise that tells my body to build and
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  Speaker 1: renew mitochondria. Then there's light exposure to optimize the mitochondrial environment.
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  Speaker 1: And then there's making sure that each complex in the
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  Speaker 1: electron transport chain has the nutrients it needs. And so
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  Speaker 1: this is a whole heap of research that I've done
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  Speaker 1: for presenting at the Mitochondrial Health Summit and other things
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  Speaker 1: like that. So firstly, let's talk about exercise and three
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  Speaker 1: forms of it. The strongest driver or signal that you
• 14:00
  Speaker 1: can send your body to build new mitochondria is to
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  Speaker 1: run it short of energy, regularly and on purpose, which
• 14:07
  Speaker 1: then switches on PGC1-alpha, the protein that we talked about
• 14:12
  Speaker 1: earlier that triggers the building of new mitochondria and the
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  Speaker 1: repair of them. So I do three kinds of training.
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  Speaker 1: The first is zone two, that boring as batshit steady
• 14:21
  Speaker 1: state stuff where you can still hold a conversation and
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  Speaker 1: that can help to build your mitochondria capacity over time.
• 14:31
  Speaker 1: and can help a little bit with mitochondrial biogenesis. But
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  Speaker 1: the second is sprint intervals, which you could replace with
• 14:37
  Speaker 1: high intensity interval training, but the sprint intervals are more
• 14:40
  Speaker 1: intense and shorter. And they give your mitochondria a very
• 14:45
  Speaker 1: strong stimulus in very little time. And it's basically character
• 14:50
  Speaker 1: building for your mitochondria. And then the third is resistance training,
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  Speaker 1: which keeps the muscle that I need when I'm 80.
• 14:57
  Speaker 1: And muscle itself is a major store of mitochondria. And
• 15:01
  Speaker 1: on mood specifically, a 2024 meta-analysis in the BMJ pulled
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  Speaker 1: 218 trials and found that any type of exercise, all
• 15:12
  Speaker 1: were more effective at reducing depression than SSRIs. And they
• 15:17
  Speaker 1: had larger benefits at higher intensities. And a recent study
• 15:23
  Speaker 1: on people 26 and under showed that resistance training was
• 15:28
  Speaker 1: at least three times more effective than antidepressants, right? So
• 15:32
  Speaker 1: that's the first thing for me, the most fundamental part.
• 15:37
  Speaker 1: You will not have healthy mitochondria if you do not
• 15:41
  Speaker 1: regularly exercise. Simple as that. The second is light. Now,
• 15:46
  Speaker 1: I get outside every morning to take my dog Soxy
• 15:49
  Speaker 1: for a walk. And it is part of my circadian
• 15:54
  Speaker 1: rhythm optimization. And it's about getting vitamin D. And partly
• 15:59
  Speaker 1: because sunlight contains red and near infrared wavelengths. And several
• 16:04
  Speaker 1: times a week, I also use a red and near
• 16:07
  Speaker 1: infrared light panel. And the reason for that is that
• 16:10
  Speaker 1: the fourth complex in the electron transport chain is an
• 16:16
  Speaker 1: enzyme called cytochrome C oxidase. That absorbs light at those wavelengths,
• 16:21
  Speaker 1: red and near infrared. And one leading theory is that
• 16:24
  Speaker 1: the light displaces nitric oxide that's been jamming up the enzyme,
• 16:29
  Speaker 1: allowing the chain to run a little faster. Now, the
• 16:33
  Speaker 1: evidence here is mixed and emerging. A few small trials
• 16:38
  Speaker 1: of near-infrared light applied to the forehead and depression have
• 16:42
  Speaker 1: been encouraging, but there was another trial using a lower
• 16:46
  Speaker 1: dose that found no benefit over a sham. So we
• 16:50
  Speaker 1: don't really know the dose, but the research is pretty
• 16:54
  Speaker 1: damn solid. We know from the research that light can
• 16:58
  Speaker 1: activate the mitochondria, that near infrared particularly penetrates deep into
• 17:04
  Speaker 1: the body and into the brain. And it plays an
• 17:07
  Speaker 1: important role in our mitochondrial function. And some researchers have
• 17:12
  Speaker 1: even produced papers showing that it has quantum effects on
• 17:16
  Speaker 1: our cells. which is a bit heavy, but I am
• 17:20
  Speaker 1: personally convinced of its importance. And if you want convincing
• 17:23
  Speaker 1: evidence that light affects mood in general, all you need
• 17:27
  Speaker 1: to do is look up seasonally affective disorder or SAD
• 17:31
  Speaker 1: and how in winter, in high latitudes, there's much greater depression.
• 17:37
  Speaker 1: So it's in Scandinavian countries. Now, let's talk about the
• 17:41
  Speaker 1: third thing, which is nutrition. And this is all about
• 17:44
  Speaker 1: supporting the electron transport chain. And once you know how
• 17:46
  Speaker 1: the chain works, the nutrients make a lot more sense.
• 17:51
  Speaker 1: So let's go through this in a sensible order. So
• 17:56
  Speaker 1: before electrons reach the chain, your food has to be
• 18:00
  Speaker 1: broken down in a series of reactions called the Krebs cycle.
• 18:03
  Speaker 1: And that cycle runs on B vitamins. So thiamine or
• 18:07
  Speaker 1: vitamin B1 is needed to move fuel from glucose into
• 18:11
  Speaker 1: the Krebs cycle in the first place. Pantothenic acid, which
• 18:15
  Speaker 1: is vitamin B5, is used to make coenzyme A, which
• 18:19
  Speaker 1: carries fuel into the cycle. Riboflavin, which is B2, and
• 18:24
  Speaker 1: niacin B3, they become the two electron carriers, FAD and NAD.
• 18:30
  Speaker 1: that collect electrons and deliver them to the actual chain.
• 18:34
  Speaker 1: And then vitamin B12 is needed too because one of
• 18:37
  Speaker 1: the cycle steps depends on it, right? Now, the first
• 18:40
  Speaker 1: complex in the electron transport chain is complex one. It
• 18:44
  Speaker 1: takes electrons from NADH. Now, this is a bit geeky,
• 18:47
  Speaker 1: but just follow me through. And NADH comes from niacin, right?
• 18:53
  Speaker 1: And passes them through a molecule called made from riboflavin.
• 18:58
  Speaker 1: And they enhance them along a series of what's called
• 19:01
  Speaker 1: iron-sulfur clusters, which need iron. Complex 2, which is also
• 19:07
  Speaker 1: part of the Krebs cycle, does a similar job using
• 19:10
  Speaker 1: FAD from riboflavin, again with iron-sulfur clusters. So we see
• 19:15
  Speaker 1: B vitamins and iron being important there. Both complexes pass
• 19:19
  Speaker 1: their electrons to coenzyme Q12, which carries them through the
• 19:24
  Speaker 1: membrane to complex 3. Now, your body makes coenzyme Q10,
• 19:30
  Speaker 1: but production declines with age and is reduced by statin drugs, right? Now,
• 19:36
  Speaker 1: I take the reduced, ready-to-use, more bioavailable form of coenzyme
• 19:41
  Speaker 1: Q12 called ubiquinol. Now, complex 3 and the small carrier
• 19:47
  Speaker 1: that follows it cytochrome c are built around heme right
• 19:52
  Speaker 1: which is the iron held in a ring structure so
• 19:55
  Speaker 1: iron is essentially gain here this is why people who
• 19:59
  Speaker 1: have iron deficiency have really low energy right because their
• 20:02
  Speaker 1: electron transport chain doesn't freaking work and then vitamin b6
• 20:07
  Speaker 1: is needed to make heme in the first place So
• 20:10
  Speaker 1: complex four cytochrome C oxidase. Now that's the enzyme that
• 20:15
  Speaker 1: my light panel and the sun both target. That needs
• 20:20
  Speaker 1: both heme iron and copper to pass the electrons onto oxygen.
• 20:24
  Speaker 1: And then finally complex five ATP synthase makes ATP. Which
• 20:30
  Speaker 1: only works in the body when it's bound to magnesium.
• 20:33
  Speaker 1: So you need magnesium as well. So. When I say
• 20:37
  Speaker 1: I take ubiquinol and a methylated B complex, the reason
• 20:41
  Speaker 1: I take methylated is just for people out there, some
• 20:45
  Speaker 1: people have problems in methylation. And taking methylated B vitamins
• 20:52
  Speaker 1: is just a bit of a safety net to make
• 20:53
  Speaker 1: sure that your thing will work properly, right? Now, I
• 20:58
  Speaker 1: make sure I also eat enough iron. I prefer to
• 21:02
  Speaker 1: get my stuff from food. It is much better to
• 21:04
  Speaker 1: get your stuff from food, right? But... I do have
• 21:06
  Speaker 1: some targeted supplements. I get my iron from food, but
• 21:10
  Speaker 1: then riboflavin, niacin, thiamine, vitamin B5, B6 and B12, they
• 21:15
  Speaker 1: keep the Krebs cycle and the first complexes running. And
• 21:19
  Speaker 1: the methylated forms of foliate and B12 are the only
• 21:23
  Speaker 1: ones that my body can use without extra conversion steps.
• 21:27
  Speaker 1: ubiquinol keeps coenzyme q12 levels up and iron sits at
• 21:32
  Speaker 1: the heart of complexes one to four and now as
• 21:35
  Speaker 1: i said i get my iron from food mostly red
• 21:37
  Speaker 1: meat some people aren't i don't eat red meat and
• 21:40
  Speaker 1: if they don't i'd urge you um and to to
• 21:43
  Speaker 1: think about it but get a blood test first because
• 21:45
  Speaker 1: too much iron can be harmful particularly for men and
• 21:49
  Speaker 1: post-menopausal women now copper and magnesium and you there are
• 21:54
  Speaker 1: um abundant in nuts seeds legumes lethe greens and dark
• 22:00
  Speaker 1: chocolate as well which i count as a bit of
• 22:02
  Speaker 1: a pleasurable intervention now the other one i want to
• 22:06
  Speaker 1: talk about the last supplement is urolithin a and that
• 22:09
  Speaker 1: targets the quality control system rather than the chain itself
• 22:13
  Speaker 1: so urolithin a is a compound your gut bacteria make
• 22:16
  Speaker 1: from polyphenols in things like pomegranates walnuts and berries Although
• 22:21
  Speaker 1: it turns out that many people don't carry the bacteria
• 22:24
  Speaker 1: needed to produce much of it. So I take it
• 22:27
  Speaker 1: directly as a bit of an insurance, right? Because it
• 22:30
  Speaker 1: switches on mitophagy, the process that clears out damaged mitochondria.
• 22:35
  Speaker 1: And in randomized trials in middle-aged and older adults, four
• 22:39
  Speaker 1: months of urolithin A improve muscle strength and endurance and
• 22:43
  Speaker 1: improve blood markers of mitochondrial health. Although not every primary
• 22:47
  Speaker 1: outcome improved in the study and it hasn't been tested,
• 22:50
  Speaker 1: I must stress this as it's a treatment for depression
• 22:53
  Speaker 1: in humans. But personally, I've seen enough evidence to put
• 22:56
  Speaker 1: it in the do good, do no harm basket. There's
• 23:00
  Speaker 1: a couple of other things worth knowing. Low vitamin D
• 23:03
  Speaker 1: is consistently linked with depression in observational studies and meta
• 23:07
  Speaker 1: analysis of supplementation trials suggest a modest benefit in people
• 23:11
  Speaker 1: who are already depressed. And a lot of depressed people
• 23:14
  Speaker 1: have low vitamin D. So it's worthwhile getting your levels checked,
• 23:17
  Speaker 1: especially in winter. And creatine, which I've talked about a lot,
• 23:21
  Speaker 1: that helps buffer the brain's energy supply. That's another one
• 23:25
  Speaker 1: to watch. In a 2025 trial, I've talked about this.
• 23:28
  Speaker 1: There was 100 people with depression. Adding five grams a
• 23:31
  Speaker 1: day of creatine to cognitive behavior therapy roughly doubled the
• 23:34
  Speaker 1: improvement compared with therapy plus a placebo, although it was
• 23:39
  Speaker 1: a small eight-week pilot study that needs to be replicated.
• 23:42
  Speaker 1: And I'd also like to see it replicated with higher
• 23:45
  Speaker 1: than five grams a day, maybe 10 to 15. And
• 23:48
  Speaker 1: then what's also really important is what you leave off
• 23:50
  Speaker 1: your plate. I've talked on numerous times in this podcast
• 23:54
  Speaker 1: about the 2020-2024 Umbrella Review in the British Medical Journal.
• 23:58
  Speaker 1: And it covered about 10 million people that found that
• 24:01
  Speaker 1: higher intake of ultra processed foods was associated with a
• 24:04
  Speaker 1: whopping 53% higher odds of common mental health disorders. Right.
• 24:11
  Speaker 1: And and we know now that it's a lot of
• 24:14
  Speaker 1: the additives in ultra processed foods that is really damaging.
• 24:18
  Speaker 1: And then fructose that we find in lots of ultra
• 24:21
  Speaker 1: processed foods, particularly soft drinks, but also in lots of others.
• 24:26
  Speaker 1: And my I did a podcast with Professor Richard Johnson
• 24:31
  Speaker 1: and his research showed that unlike other nutrients, fructose actually
• 24:35
  Speaker 1: lowers the available energy inside cells and causes a mitochondrial
• 24:41
  Speaker 1: energy crisis particularly when you have a bucket load of
• 24:45
  Speaker 1: of fructose as people do when they're drinking soft drinks
• 24:48
  Speaker 1: and having lots of ultra processed foods and so if
• 24:50
  Speaker 1: you want to go deeper on that and just search
• 24:52
  Speaker 1: my podcast with professor richard johnson it's a cracker so
• 24:56
  Speaker 1: put together and Exercise tells your body to build and
• 25:01
  Speaker 1: renew the mitochondria. Light helps the chain to run more efficiently.
• 25:07
  Speaker 1: Nutrients make sure each complex has what it needs. And
• 25:10
  Speaker 1: Neuralithin A can help to clear out the damaged ones.
• 25:13
  Speaker 1: But of all of these... exercise has by far the
• 25:17
  Speaker 1: strongest evidence and does most of the work so there's
• 25:21
  Speaker 1: a rather long podcast but i think it's a pretty
• 25:22
  Speaker 1: important one so so let me just do a quick
• 25:25
  Speaker 1: takeaway the stoics which you know i'm a big fan
• 25:27
  Speaker 1: of they drew a hard line between what's up to
• 25:30
  Speaker 1: us and what isn't and epictetus would have found plenty
• 25:34
  Speaker 1: to work with in this research your genes aren't up
• 25:37
  Speaker 1: to you Much of the stress that lands on your
• 25:40
  Speaker 1: desk this week isn't up to you. And whether you
• 25:42
  Speaker 1: end up in a depressive episode isn't entirely up to
• 25:45
  Speaker 1: you either. But a surprising amount of what determines how
• 25:49
  Speaker 1: well your mitochondria function sits on the sign of what
• 25:52
  Speaker 1: you can control. How much you move, whether or not
• 25:55
  Speaker 1: you get daylight and what you eat and what you
• 25:58
  Speaker 1: don't eat as well. And that's a pretty damn good
• 26:00
  Speaker 1: reason to invest. in the parts of the system that
• 26:04
  Speaker 1: you can influence so that you have more capacity when
• 26:08
  Speaker 1: life gets hard. So a couple of takeaways to finish. First,
• 26:12
  Speaker 1: think of your brain as an energy system as well
• 26:14
  Speaker 1: as a chemical one. Low mood and low energy often
• 26:17
  Speaker 1: go together and looking after your energy supply is a
• 26:20
  Speaker 1: really important part of looking after your mind. Second, exercise
• 26:24
  Speaker 1: matters the most. It is the one intervention that builds
• 26:27
  Speaker 1: new mitochondria recycles others and has very strong evidence for
• 26:31
  Speaker 1: lifting mood and it costs nothing but effort so if
• 26:34
  Speaker 1: you only change one thing it's about this and then
• 26:37
  Speaker 1: third is about feeding the chain b vitamins iron copper
• 26:41
  Speaker 1: magnesium and coenzyme q10 particularly in the ubiquinol form eats
• 26:46
  Speaker 1: have specific roles and so get them from food first
• 26:50
  Speaker 1: test before you supplement And then if you need to
• 26:54
  Speaker 1: add some supplements in. And then everything else, including my
• 26:59
  Speaker 1: light panel and NeuroLift in the A, treat them as
• 27:02
  Speaker 1: promising rather than proven interventions. But for me, I think
• 27:06
  Speaker 1: there's enough evidence of all of this to suggest that
• 27:10
  Speaker 1: looking after your mitochondria can improve your overall health and
• 27:15
  Speaker 1: help you to optimize your mood. That's it for this week, folks.
• 27:20
  Speaker 1: Catch you next time. Hey!