1 00:00:09,880 --> 00:00:14,080 Speaker 1: Hey, everybody, Welcome to another edition of Wisdom Wednesdays, and 2 00:00:14,200 --> 00:00:18,640 Speaker 1: today I am going to explore a very interesting new 3 00:00:18,800 --> 00:00:25,080 Speaker 1: study that shows a psychophysiological approach to mental health is 4 00:00:25,200 --> 00:00:30,760 Speaker 1: more effective than a psychological approach on its own. So depression. 5 00:00:30,760 --> 00:00:32,960 Speaker 1: We're going to talk about depression here. It affects more 6 00:00:33,000 --> 00:00:36,559 Speaker 1: than three hundred and fifty million people globally, and it 7 00:00:36,640 --> 00:00:39,199 Speaker 1: is difficult to treat, with up to one third of 8 00:00:39,240 --> 00:00:45,240 Speaker 1: patients not responding to psychotherapy or antidepressants, and many can 9 00:00:45,400 --> 00:00:50,040 Speaker 1: discontinuing and the treatment due to adverse effects, and they're 10 00:00:50,120 --> 00:00:53,440 Speaker 1: mostly from the antidepressants, but there are also some adverse 11 00:00:53,440 --> 00:00:58,400 Speaker 1: effects of psychotherapy. Now, Creating monohydrate, which you'll have to 12 00:00:58,400 --> 00:01:02,120 Speaker 1: heard me talk about before, is a very well researched 13 00:01:02,200 --> 00:01:06,880 Speaker 1: sports supplement. It's good for muscular performance and recovery, and 14 00:01:07,240 --> 00:01:09,880 Speaker 1: you may have heard me talk about its effect on 15 00:01:10,080 --> 00:01:13,680 Speaker 1: brain function. It has recently been shown to have a 16 00:01:13,720 --> 00:01:17,960 Speaker 1: positive effect on brain function, and it is inexpensive and 17 00:01:18,000 --> 00:01:20,840 Speaker 1: it's very very safe. It's had lots of studies done 18 00:01:20,840 --> 00:01:24,800 Speaker 1: on its safety, and as I said, it's attracted recent 19 00:01:24,840 --> 00:01:29,280 Speaker 1: attention because of its role in brain energy metabolism, and 20 00:01:29,520 --> 00:01:33,880 Speaker 1: it's documented antidepressant like effects in pre clinical studies. And 21 00:01:33,920 --> 00:01:36,280 Speaker 1: I think I've talked about this before. It's the study 22 00:01:36,319 --> 00:01:39,560 Speaker 1: that showed that it was a small study, but it 23 00:01:39,640 --> 00:01:42,800 Speaker 1: showed that creating was quite effective on its own as 24 00:01:42,840 --> 00:01:48,840 Speaker 1: an antidepressant. Now, research shows that individuals with depression often 25 00:01:49,000 --> 00:01:53,920 Speaker 1: have lower brain creating levels. They also have imperred cellular 26 00:01:54,120 --> 00:02:01,400 Speaker 1: energy regulation and altered monomine functioning, so monomine being dopamine, 27 00:02:01,440 --> 00:02:04,760 Speaker 1: serotonin and no adrenaline or if you're in America that's 28 00:02:04,800 --> 00:02:08,760 Speaker 1: nowhere epinephrine. And there have been a number of small 29 00:02:08,840 --> 00:02:13,440 Speaker 1: clinical trials that suggest that creating can actually enhance the 30 00:02:13,480 --> 00:02:17,520 Speaker 1: effects of antidepressant drugs, but almost all of those didn't 31 00:02:17,520 --> 00:02:21,840 Speaker 1: have a placebo control, and none of them have investigated 32 00:02:21,960 --> 00:02:27,960 Speaker 1: creating as an adjunct to psychotherapy, particularly CBT now because 33 00:02:28,120 --> 00:02:32,680 Speaker 1: CBT cognitive behavior therapy itself actually requires quite a lot 34 00:02:32,720 --> 00:02:36,480 Speaker 1: of cognitive resources, because you've got to have really good 35 00:02:36,520 --> 00:02:39,320 Speaker 1: attention on your thoughts, you're going to have good working memory, 36 00:02:39,320 --> 00:02:42,760 Speaker 1: and then there's behavioral activation, which all of those require 37 00:02:42,800 --> 00:02:49,000 Speaker 1: cognitive resources, and creating's impact on brain energy metabolism might 38 00:02:49,080 --> 00:02:54,440 Speaker 1: theoretically promote better engagement and improve outcomes and this study 39 00:02:55,240 --> 00:03:00,200 Speaker 1: that has very recently been published in the European the 40 00:03:00,240 --> 00:03:07,760 Speaker 1: Journal of European Neuropsychopharmacology, investigated just that they wanted to 41 00:03:07,800 --> 00:03:13,960 Speaker 1: test whether adding creating to CBT improved depressive symptoms versus 42 00:03:13,960 --> 00:03:17,679 Speaker 1: CBT alone, and they also wanted to look at it's 43 00:03:18,000 --> 00:03:21,079 Speaker 1: the feasibility of doing it, it's tolerability, and its safety. 44 00:03:21,320 --> 00:03:26,520 Speaker 1: So they conducted an eight week double blind randomized placebo 45 00:03:26,600 --> 00:03:29,560 Speaker 1: control trial. And what that means double blind means that 46 00:03:29,600 --> 00:03:32,280 Speaker 1: the individuals didn't know what they were taking. Some of 47 00:03:32,320 --> 00:03:34,400 Speaker 1: them were taking creating, some of them were taking a 48 00:03:34,440 --> 00:03:37,880 Speaker 1: placebo that they thought was creating. But the researchers also 49 00:03:37,920 --> 00:03:42,960 Speaker 1: didn't know. And this is important because researchers can either 50 00:03:43,040 --> 00:03:47,240 Speaker 1: sometimes deliberately if they're a bit dodgy, or just kind 51 00:03:47,280 --> 00:03:52,880 Speaker 1: of accidentally, you know, in encourage people are having have 52 00:03:53,120 --> 00:03:57,040 Speaker 1: biases towards the people who are getting the intervention if 53 00:03:57,080 --> 00:03:59,920 Speaker 1: they know who's getting the intervention. So double blind is 54 00:04:00,040 --> 00:04:03,600 Speaker 1: the gold standard. And they did it with one hundred adults, 55 00:04:03,600 --> 00:04:06,640 Speaker 1: so pretty good sample size. Their men age was thirty 56 00:04:07,760 --> 00:04:10,120 Speaker 1: and this was in India, and they met all of 57 00:04:10,160 --> 00:04:14,120 Speaker 1: the participants met the DSM five criteria. For major depression. 58 00:04:14,160 --> 00:04:16,640 Speaker 1: So we're not talking mindary depression. This is major depression. 59 00:04:17,160 --> 00:04:20,680 Speaker 1: They had PHQ nine scores of greater than five. That's 60 00:04:20,720 --> 00:04:26,000 Speaker 1: a depressive depression survey, and they were not taking a 61 00:04:26,240 --> 00:04:30,960 Speaker 1: psychotropic medication. They were then randomized to a group that 62 00:04:31,120 --> 00:04:35,080 Speaker 1: got creating plus CBT, and they got five grams a 63 00:04:35,160 --> 00:04:39,760 Speaker 1: day of oral creating monohydrate plus. They got bi weekly, 64 00:04:39,839 --> 00:04:45,839 Speaker 1: so once a fortnite individual CBT sessions with the psychotherapist 65 00:04:46,480 --> 00:04:50,120 Speaker 1: and then the placebo group they had five grams a 66 00:04:50,200 --> 00:04:55,400 Speaker 1: day of starch placebo and in the same CBT protocol. 67 00:04:55,600 --> 00:04:57,880 Speaker 1: I wonder why they did five grams a day because 68 00:04:58,160 --> 00:05:02,400 Speaker 1: recent research has shown that actually optimizing brain function is 69 00:05:02,440 --> 00:05:04,520 Speaker 1: up there about twenty grams a day. So I love 70 00:05:04,640 --> 00:05:07,159 Speaker 1: to have seen them. Maybe they'll do other studies where 71 00:05:07,120 --> 00:05:10,680 Speaker 1: they'll give a higher dose because some researchers think that 72 00:05:10,760 --> 00:05:12,600 Speaker 1: for a lot of the first five grams is going 73 00:05:12,640 --> 00:05:15,840 Speaker 1: to get hoovered up by the muscle. But anyway, so 74 00:05:15,880 --> 00:05:21,080 Speaker 1: the CBT was delivered at weeks zero, two, four, six, 75 00:05:21,279 --> 00:05:27,640 Speaker 1: and eight by a registered clinical psychologist and they actually 76 00:05:27,760 --> 00:05:32,919 Speaker 1: used Be's low intensity CBT model that consisted of psycho education, 77 00:05:33,720 --> 00:05:39,040 Speaker 1: cognitive restructuring, and behavioral activation actually getting shit done. Outcomes 78 00:05:39,040 --> 00:05:42,719 Speaker 1: were measured at each visit and they included doing the 79 00:05:42,880 --> 00:05:49,120 Speaker 1: PHQ nine again and asking them about adverse events and 80 00:05:49,200 --> 00:05:53,400 Speaker 1: the results. Then, both groups showed meaningful improvement in depression, 81 00:05:53,680 --> 00:05:58,800 Speaker 1: which is consistent with typical CBT effects. However, the creating 82 00:05:59,000 --> 00:06:05,680 Speaker 1: plus CBT group almost doubled the effectiveness the PHQ nine 83 00:06:06,120 --> 00:06:09,400 Speaker 1: reduced to five point eight that's in the mild range 84 00:06:09,760 --> 00:06:13,279 Speaker 1: in the creating arm, versus eleven point nine which is 85 00:06:13,360 --> 00:06:17,280 Speaker 1: moderate range in the placebo orm. Now, this is this 86 00:06:17,360 --> 00:06:22,479 Speaker 1: is what we call clinical significance, right, And often when 87 00:06:22,480 --> 00:06:26,720 Speaker 1: they look at antidepressants, they have statistical significance, but not 88 00:06:26,920 --> 00:06:32,760 Speaker 1: clinical significance. Clinical significance means does the individual notice a 89 00:06:32,880 --> 00:06:37,920 Speaker 1: significant difference in themselves, not fancy statistics. Does the individual notice? 90 00:06:38,040 --> 00:06:43,039 Speaker 1: And going from moderate to mild would certainly be clinical significance. 91 00:06:44,120 --> 00:06:48,440 Speaker 1: So this is pretty damn good. I think it's a 92 00:06:48,440 --> 00:06:52,359 Speaker 1: pretty amazing study that you can double the effectiveness of 93 00:06:52,440 --> 00:06:57,120 Speaker 1: CBT just by abbing five grams a day of creating, 94 00:06:58,200 --> 00:07:01,720 Speaker 1: And like I said, if they did more, I suspect 95 00:07:01,720 --> 00:07:05,200 Speaker 1: there might even be a bigger thing. Now, drop out 96 00:07:05,320 --> 00:07:09,920 Speaker 1: rates were high about forty percent in both arms. Likely 97 00:07:10,000 --> 00:07:13,400 Speaker 1: influenced by COVID nineteen disruptions because this was actually the 98 00:07:13,440 --> 00:07:15,560 Speaker 1: study took place during when there was a lot of 99 00:07:15,560 --> 00:07:19,720 Speaker 1: COVID around, but there weren't different between groups, right, So 100 00:07:20,200 --> 00:07:23,640 Speaker 1: I think they're probably suggesting that it was COVID. It 101 00:07:23,880 --> 00:07:28,120 Speaker 1: wasn't the intervention itself. Adverse events were common, but mild 102 00:07:28,600 --> 00:07:31,200 Speaker 1: and similar in total number. There was a bit of 103 00:07:31,240 --> 00:07:37,160 Speaker 1: gas owintestinal symptoms, constipation, diarrhea, dominald discomfort, and muscle cramps 104 00:07:37,640 --> 00:07:41,800 Speaker 1: were somewhat more frequent in the creating group, so some 105 00:07:41,880 --> 00:07:44,720 Speaker 1: of the placebo group actually got some of these things, 106 00:07:45,600 --> 00:07:49,240 Speaker 1: but they weren't significant side effects. There was no episodes 107 00:07:49,280 --> 00:07:53,760 Speaker 1: of suicidality or mania actually occurred, So one of the 108 00:07:53,800 --> 00:07:58,320 Speaker 1: researchers think was going on. There's this few biological and 109 00:07:58,440 --> 00:08:03,160 Speaker 1: cognitive mechanisms that could explain the additive effect of creating. 110 00:08:03,520 --> 00:08:07,000 Speaker 1: The first I alluded to at the start, which has 111 00:08:07,080 --> 00:08:11,360 Speaker 1: improved brain energy metabolism. So creating, if you don't know 112 00:08:12,520 --> 00:08:17,880 Speaker 1: that increases FOSPHL creating availability and ATP buffering. So ATP 113 00:08:18,080 --> 00:08:22,000 Speaker 1: is the energy currency, and one of our energy systems 114 00:08:22,320 --> 00:08:26,600 Speaker 1: is the ATPPC system. Fosphil creating, and then we have 115 00:08:26,640 --> 00:08:30,720 Speaker 1: aerobic and then we have anaerobic. So basically the extra 116 00:08:30,800 --> 00:08:36,239 Speaker 1: creating supported the energy demands of the neurons. Depressed individuals 117 00:08:36,400 --> 00:08:42,720 Speaker 1: often show reduced prefrontal creating. This is really significant. And 118 00:08:42,760 --> 00:08:48,160 Speaker 1: then the supplementation obviously may well restore metabolic function in 119 00:08:48,360 --> 00:08:53,240 Speaker 1: regions necessary for emotional regulation and the cognitive work that's 120 00:08:53,320 --> 00:08:57,600 Speaker 1: required for CBT. The next thing is the modulation of 121 00:08:57,640 --> 00:09:01,320 Speaker 1: the monomine systems, so that's the serotonin, the dopamine, the 122 00:09:01,360 --> 00:09:06,680 Speaker 1: nohare adrenaline slash no epinephyrine in antidepressant treatments. Right. Then 123 00:09:07,000 --> 00:09:12,120 Speaker 1: the other suggestion was there's neuroprotective effects. Creatine actually reduces 124 00:09:12,160 --> 00:09:17,479 Speaker 1: oxidative stress, it reduces apoptosis or cell death, it reduces neuroinflammation, 125 00:09:18,000 --> 00:09:22,280 Speaker 1: and they are all implicated in the pathophysiology of depression. 126 00:09:22,840 --> 00:09:26,720 Speaker 1: And then the last one and possible mechanism is facilitation 127 00:09:26,840 --> 00:09:31,160 Speaker 1: of cognitive processes. So there's one other randomized control trial 128 00:09:31,200 --> 00:09:35,840 Speaker 1: that reported cognitive improvements with creating in bipolar depression, and 129 00:09:36,040 --> 00:09:42,760 Speaker 1: enhance cognitive flexibility or working memory may well amplify cbt's effectiveness. 130 00:09:43,240 --> 00:09:49,160 Speaker 1: So in conclusion, this for me is more evidence that 131 00:09:49,679 --> 00:09:55,199 Speaker 1: we can't just have a psychological approach to mood disorders. 132 00:09:55,480 --> 00:10:02,280 Speaker 1: We need to have a psychophysiological because the physiology is 133 00:10:02,360 --> 00:10:08,720 Speaker 1: hugely important and in fact outperforms psychotherapy. It outperforms antidepressant 134 00:10:08,960 --> 00:10:11,920 Speaker 1: when you take exercise alone, it outperforms all of those 135 00:10:12,640 --> 00:10:15,920 Speaker 1: creating is as effective as antidepressants. And here you can 136 00:10:15,960 --> 00:10:19,960 Speaker 1: see it's doubling the effect of CBT. And you add 137 00:10:20,000 --> 00:10:23,640 Speaker 1: in sleep, hygiene, good food, all of those things, it 138 00:10:23,679 --> 00:10:28,760 Speaker 1: will be so much more effective than just doing psychotherapy 139 00:10:28,920 --> 00:10:33,000 Speaker 1: or antidepressants. So this is yet another research paper that 140 00:10:33,520 --> 00:10:38,720 Speaker 1: is really calling for that integrated approach to mental health 141 00:10:38,720 --> 00:10:42,360 Speaker 1: disorders and not just looking at the brain or the 142 00:10:42,480 --> 00:10:47,600 Speaker 1: mind as this isolated part of the system, because nothing 143 00:10:47,679 --> 00:10:50,319 Speaker 1: is isolated in the system, that is the human being. 144 00:10:50,880 --> 00:10:53,840 Speaker 1: So that's it for this week, folks, catch you next time.