1
00:00:09,000 --> 00:00:11,320
Speaker 1: Doctor Charge Brenner, Welcome to the podcast.

2
00:00:11,920 --> 00:00:14,160
Speaker 2: It is a pleasure to be with you.

3
00:00:13,240 --> 00:00:17,040
Speaker 1: You know, I have been waiting for you or someone

4
00:00:17,239 --> 00:00:19,919
Speaker 1: like you for a little bit of time, right and

5
00:00:20,040 --> 00:00:22,960
Speaker 1: for our listeners, for the benefit of it. We are

6
00:00:23,000 --> 00:00:26,440
Speaker 1: going to talk about all things n A D plus

7
00:00:27,040 --> 00:00:30,960
Speaker 1: and so NMN and are And some people might be going,

8
00:00:31,000 --> 00:00:33,159
Speaker 1: what the hell is he talking about? And other listeners

9
00:00:33,200 --> 00:00:37,400
Speaker 1: are going, oh, yes, I know that the longevity molecules.

10
00:00:38,040 --> 00:00:40,720
Speaker 1: So you are an expert.

11
00:00:40,479 --> 00:00:44,600
Speaker 2: There through the molecules of life. You know, there's certainly

12
00:00:44,640 --> 00:00:52,200
Speaker 2: the molecules of metabolism, the central jewels of metabolism, and

13
00:00:53,360 --> 00:00:57,120
Speaker 2: probably the most evidence based supplement that has been discovered

14
00:00:57,160 --> 00:00:58,480
Speaker 2: in the last fifty years.

15
00:00:59,040 --> 00:01:02,280
Speaker 1: That is a interesting that you say, probably the most

16
00:01:02,280 --> 00:01:05,759
Speaker 1: evidence best supplement in the last fifty years. Because I'll

17
00:01:05,880 --> 00:01:09,720
Speaker 1: just set this up for the listeners. So I heard

18
00:01:09,760 --> 00:01:14,400
Speaker 1: about NAD plus, MN and n R years ago, like

19
00:01:14,440 --> 00:01:17,520
Speaker 1: lots of people who are into longevity, you know, it's

20
00:01:17,640 --> 00:01:22,640
Speaker 1: all over the internet, and I had started taking MMn

21
00:01:23,240 --> 00:01:26,120
Speaker 1: and then I just thought one day, jeez, I haven't

22
00:01:26,120 --> 00:01:29,560
Speaker 1: actually done my due diligence on this, and I had

23
00:01:29,560 --> 00:01:34,160
Speaker 1: the little ghost of resveratrol in the back of my goodness.

24
00:01:35,080 --> 00:01:41,119
Speaker 2: Can we reworkwind and reset the whole thing, because if

25
00:01:41,160 --> 00:01:44,199
Speaker 2: you saw the itch that I got the first time

26
00:01:44,240 --> 00:01:49,600
Speaker 2: that you said longevity. Yes, I'm just uncomfortable about the

27
00:01:49,640 --> 00:01:55,480
Speaker 2: framing from the beginning, and I'm super uncomfortable about the

28
00:01:55,520 --> 00:02:01,680
Speaker 2: connection with rosveratrol, the framing around certain ruins around people

29
00:02:01,800 --> 00:02:07,440
Speaker 2: not having to age. They're being single, dominantly acting genes

30
00:02:07,480 --> 00:02:14,519
Speaker 2: that you know that preserve you know, human life. And

31
00:02:15,440 --> 00:02:19,239
Speaker 2: i just want to tell you that I'm a metabolism scientist.

32
00:02:20,040 --> 00:02:22,600
Speaker 2: The stuff I work on, it is real. You know.

33
00:02:23,639 --> 00:02:28,160
Speaker 2: The NAD system is disturbed in probably a dozen different

34
00:02:28,160 --> 00:02:34,160
Speaker 2: conditions of metabolic stress that are intrinsically associated with repair

35
00:02:35,440 --> 00:02:41,760
Speaker 2: and anti inflammatory pathways, resistance to infection, getting through time

36
00:02:41,840 --> 00:02:46,800
Speaker 2: zone disruption. Now there's an evidence basis not only for

37
00:02:46,919 --> 00:02:52,760
Speaker 2: anti inflammation, but for healthy aging with peripheral artery disease,

38
00:02:52,840 --> 00:02:58,960
Speaker 2: which might be the central ten million person presentation of

39
00:02:59,000 --> 00:03:03,800
Speaker 2: age related disease in the United States. But I'm uncomfortable

40
00:03:04,120 --> 00:03:08,040
Speaker 2: with a lot of the literature, okay, And so what

41
00:03:08,080 --> 00:03:10,240
Speaker 2: I'd like to do is if we could take people

42
00:03:11,280 --> 00:03:14,840
Speaker 2: you know on the journey and start with what NAD is,

43
00:03:15,919 --> 00:03:19,720
Speaker 2: and how it gets disrupted, and what the use cases

44
00:03:19,760 --> 00:03:21,640
Speaker 2: of NR is. But I'm not going to be the

45
00:03:21,680 --> 00:03:25,079
Speaker 2: guy that tells you that you won't age, or you're

46
00:03:25,080 --> 00:03:28,840
Speaker 2: going to live forever, or that your surtoins are going

47
00:03:28,919 --> 00:03:35,240
Speaker 2: to be activated. And I'll never recommend resveratrol. And I'll

48
00:03:35,320 --> 00:03:38,280
Speaker 2: explain the difference between n R and NMN and an

49
00:03:38,320 --> 00:03:41,680
Speaker 2: A D. But there's there's a lot of misinformation out there.

50
00:03:42,680 --> 00:03:46,400
Speaker 1: All look absolutely charged. And I didn't mean to connect

51
00:03:46,720 --> 00:03:50,920
Speaker 1: res vitral to NADA. I was just talking about my experience, right,

52
00:03:51,600 --> 00:03:53,400
Speaker 1: some of my listeners will have will have heard me

53
00:03:53,480 --> 00:03:56,200
Speaker 1: talk about this before because I've been taking res virtual.

54
00:03:56,240 --> 00:04:00,000
Speaker 1: You know, again, it was a molecule tited on the Internet,

55
00:04:00,200 --> 00:04:03,360
Speaker 1: not in the circles you work in, but it was though.

56
00:04:03,680 --> 00:04:08,480
Speaker 2: But it did come out of of of major labs.

57
00:04:08,640 --> 00:04:09,920
Speaker 2: I mean that it came out.

58
00:04:09,800 --> 00:04:12,160
Speaker 1: Of Harvard, That's true. It came out of Harvard and

59
00:04:12,240 --> 00:04:15,720
Speaker 1: David Sinclair and then he sold his research to GSK

60
00:04:17,640 --> 00:04:20,160
Speaker 1: or his company, and then they couldn't replicate the research

61
00:04:20,200 --> 00:04:23,159
Speaker 1: and all of this. Now, the reason why I just

62
00:04:23,240 --> 00:04:29,040
Speaker 1: made the connection, right is that I was taking NMN.

63
00:04:29,120 --> 00:04:33,640
Speaker 1: I'd started taking NMN just based on the idea that

64
00:04:33,880 --> 00:04:38,160
Speaker 1: it was active in pathways that were important. Right. And

65
00:04:38,200 --> 00:04:42,120
Speaker 1: then I thought, let me look at the the literature,

66
00:04:42,440 --> 00:04:47,000
Speaker 1: the human literature on MNN and NR, and it wasn't

67
00:04:47,040 --> 00:04:50,040
Speaker 1: there at the time, right. And I but I've said,

68
00:04:50,480 --> 00:04:54,200
Speaker 1: this is something that I'm watching very very closely because

69
00:04:54,920 --> 00:04:57,839
Speaker 1: NAD and NAD plus and its role in the body.

70
00:04:57,960 --> 00:05:03,200
Speaker 1: I am completely convinced the bike. I'm just haven't quite

71
00:05:03,360 --> 00:05:06,800
Speaker 1: made the leap of feast that if it gets low

72
00:05:06,839 --> 00:05:09,120
Speaker 1: and you can take a supplement and it raises it,

73
00:05:09,279 --> 00:05:12,680
Speaker 1: is it going to have significantly better outcomes?

74
00:05:12,960 --> 00:05:16,040
Speaker 2: Intend to take a leap of faith. Yes, yeah, And

75
00:05:16,440 --> 00:05:19,400
Speaker 2: I want you to take a leap with me of evidence,

76
00:05:19,760 --> 00:05:26,359
Speaker 2: you know. And and and the thing is that the

77
00:05:26,480 --> 00:05:33,120
Speaker 2: same people that promoted resveratrol are in fact promoting an

78
00:05:33,160 --> 00:05:38,520
Speaker 2: a man, and a man is actually working. It's It's

79
00:05:38,600 --> 00:05:41,880
Speaker 2: strange because NMN is n R with a phosphate group

80
00:05:41,960 --> 00:05:45,920
Speaker 2: on it, but when you take it orally, it goes

81
00:05:46,160 --> 00:05:48,479
Speaker 2: back to n R before it can get into cells.

82
00:05:48,520 --> 00:05:54,200
Speaker 2: So MN is weirdly a precursor of n R because

83
00:05:54,240 --> 00:05:56,679
Speaker 2: then it gets into cells and gets converted to nimn

84
00:05:56,760 --> 00:06:01,600
Speaker 2: and then nad co enzymes so enemen and are basically

85
00:06:01,640 --> 00:06:07,240
Speaker 2: working on the same pathways in the body. The folks

86
00:06:07,279 --> 00:06:13,320
Speaker 2: that brought you, you know, risveratrol as a mass marketed supplement.

87
00:06:13,360 --> 00:06:15,520
Speaker 2: Of course, it was kind of in the food supply

88
00:06:15,600 --> 00:06:19,400
Speaker 2: for a long time because it's famously in red wine

89
00:06:19,480 --> 00:06:24,520
Speaker 2: and it's in peanuts and other stuff. Their use case

90
00:06:24,600 --> 00:06:28,760
Speaker 2: for it was it activates these genes called sirtuins. Right,

91
00:06:30,640 --> 00:06:36,039
Speaker 2: Certuins are not conserved longevity genes. They're not even conserved

92
00:06:36,080 --> 00:06:40,279
Speaker 2: as longevity genes in yeast. As it turns out if

93
00:06:40,320 --> 00:06:44,200
Speaker 2: you just look at how long yeast cells live without

94
00:06:44,279 --> 00:06:47,200
Speaker 2: and with the sertu gene, they live longer if they

95
00:06:47,240 --> 00:06:51,320
Speaker 2: don't have the sertugene. So, even back in yeast that

96
00:06:53,080 --> 00:06:56,719
Speaker 2: the research was not really sound and it was very

97
00:06:56,800 --> 00:07:03,240
Speaker 2: selectively presented, and then it didn't really replicate in worms

98
00:07:03,279 --> 00:07:06,320
Speaker 2: and flies, even though there were some papers in the

99
00:07:06,360 --> 00:07:10,080
Speaker 2: early two thousands that said that extra copies of certu

100
00:07:10,240 --> 00:07:13,320
Speaker 2: genes extends lifespan and animals, and as you know, it

101
00:07:13,960 --> 00:07:19,240
Speaker 2: doesn't work in mice and doesn't work in humans. So however,

102
00:07:20,640 --> 00:07:24,720
Speaker 2: any D and the four anyd coenzymes, and you know

103
00:07:24,760 --> 00:07:27,920
Speaker 2: what they are an a D plus, any dh, ADP plus,

104
00:07:27,960 --> 00:07:32,320
Speaker 2: and an aph. These are the central catalysts of metabolism, right,

105
00:07:32,840 --> 00:07:37,520
Speaker 2: so they move high energy electrons. We take in food

106
00:07:37,560 --> 00:07:41,040
Speaker 2: that has calories, protein, fat, and carbohydrate. It gets to

107
00:07:41,040 --> 00:07:48,880
Speaker 2: be broken down into intermediates like pyravd and alplacated glutorate

108
00:07:49,040 --> 00:07:52,040
Speaker 2: and the ketyl CoA, and some of it gets fully

109
00:07:52,120 --> 00:07:58,760
Speaker 2: oxidized generating ATP. Other stuff goes into those intermediate compounds

110
00:07:58,880 --> 00:08:03,360
Speaker 2: like pyrivate, allen in, alphacita, gluot rate and gets built

111
00:08:03,480 --> 00:08:09,040
Speaker 2: up into making new lipids, right, making nucleotides that requires

112
00:08:09,040 --> 00:08:14,720
Speaker 2: the nadph and the NAD system comes under attack in

113
00:08:14,840 --> 00:08:20,200
Speaker 2: many conditions of metabolic stress. So use case of NAD

114
00:08:21,600 --> 00:08:28,400
Speaker 2: is basically fighting these conditions of metabolic stress and repleting.

115
00:08:28,480 --> 00:08:34,199
Speaker 2: We're kind of rebuilding the NAD system inside various types

116
00:08:34,240 --> 00:08:41,120
Speaker 2: of cells. Hepatocytes, nerve cells, immune cells in order to

117
00:08:41,200 --> 00:08:48,760
Speaker 2: be able to damp down on overactive innate immune responses,

118
00:08:50,480 --> 00:08:58,880
Speaker 2: promote DNA repair, promote tissue repair, and just because ultimately

119
00:08:58,920 --> 00:09:03,000
Speaker 2: we're not interested in improving the health of mice and

120
00:09:03,040 --> 00:09:07,520
Speaker 2: the laboratory, I'll tell you that there's eight randomized clinical

121
00:09:07,559 --> 00:09:12,559
Speaker 2: trials that show anti inflammatory activity of NR oral NR.

122
00:09:13,160 --> 00:09:15,680
Speaker 1: In human beings and humans and jesting.

123
00:09:16,640 --> 00:09:21,760
Speaker 2: But and I'm going to start mentioning this this more.

124
00:09:22,240 --> 00:09:27,520
Speaker 2: There's a really important positive result in peripheral artery disease. Okay,

125
00:09:28,160 --> 00:09:30,760
Speaker 2: And the reason that I'm going to mention this more

126
00:09:31,679 --> 00:09:35,960
Speaker 2: is the quality of the and the independence of the

127
00:09:36,000 --> 00:09:40,040
Speaker 2: research group that is running these trials. So this is

128
00:09:40,280 --> 00:09:48,080
Speaker 2: from Professor McDermott's group at Northwestern University, probably the number

129
00:09:48,160 --> 00:09:52,600
Speaker 2: one clinical trialists in the area of peripheral artery disease.

130
00:09:53,440 --> 00:09:59,160
Speaker 2: So you know, ten million US citizens alone, and so

131
00:09:59,440 --> 00:10:02,240
Speaker 2: hundreds of million, maybe one hundred million around the world

132
00:10:02,600 --> 00:10:06,280
Speaker 2: have peripheral artery disease. A lot of them are smokers,

133
00:10:06,760 --> 00:10:13,600
Speaker 2: almost all of them are older. There's signs of you know, atherosclerosis,

134
00:10:14,640 --> 00:10:23,679
Speaker 2: you know, worse circulation. And at minimum, these people are

135
00:10:23,760 --> 00:10:34,120
Speaker 2: experiencing pain, loss of mobility, poor recovery from what you

136
00:10:34,200 --> 00:10:38,320
Speaker 2: and I would consider mild exertion. But if they get

137
00:10:38,320 --> 00:10:40,920
Speaker 2: a cut or infection, they could get a wounds that

138
00:10:40,960 --> 00:10:47,440
Speaker 2: doesn't heal, and they could get to a point where

139
00:10:47,480 --> 00:10:52,679
Speaker 2: something's amputated. Okay. The men typically have a reptile dysfunction,

140
00:10:53,320 --> 00:10:56,240
Speaker 2: So this is a this is a major age related

141
00:10:56,640 --> 00:11:01,640
Speaker 2: condition and the type of condition where the primary endpoint

142
00:11:01,920 --> 00:11:06,160
Speaker 2: in a randomized clinical trial is walking speed. Yeah, what

143
00:11:06,240 --> 00:11:07,600
Speaker 2: can you do in six minutes?

144
00:11:08,080 --> 00:11:11,280
Speaker 1: Yeah? Right? And it's just for the for the individuals

145
00:11:11,559 --> 00:11:17,040
Speaker 1: that the walking speed is clearly something that that is

146
00:11:17,280 --> 00:11:21,240
Speaker 1: massively influenced by peripheral artery disease because you're just not

147
00:11:21,320 --> 00:11:24,800
Speaker 1: getting blood flow. So if you can't get proper blood flow,

148
00:11:25,280 --> 00:11:28,840
Speaker 1: your muscles don't work effectively. So it's one of those

149
00:11:28,880 --> 00:11:32,319
Speaker 1: things like walking speed is a big predictor of one

150
00:11:32,320 --> 00:11:34,160
Speaker 1: of the big predictors of how long you're going to live.

151
00:11:34,320 --> 00:11:39,400
Speaker 2: Right, you can take you can take every publication on

152
00:11:40,480 --> 00:11:49,000
Speaker 2: DNA methylation age tests and glycan age tests and other

153
00:11:49,200 --> 00:11:54,600
Speaker 2: biomarker age tests, and you can put them in one pile, okay,

154
00:11:55,360 --> 00:12:02,000
Speaker 2: and then you give me a function assay, like a

155
00:12:02,080 --> 00:12:05,960
Speaker 2: six minute walking speed, and I prefer that functional assay

156
00:12:06,559 --> 00:12:11,480
Speaker 2: to any forest full. You could cut down an entire

157
00:12:11,559 --> 00:12:17,880
Speaker 2: forest to pivot to publish the papers on methylation based

158
00:12:17,960 --> 00:12:22,040
Speaker 2: age tests tests, and they don't matter as much as

159
00:12:22,160 --> 00:12:26,000
Speaker 2: one good test of walking speed because walking speed is

160
00:12:26,040 --> 00:12:30,079
Speaker 2: what you what you can do, yes, and walking speed,

161
00:12:30,280 --> 00:12:34,320
Speaker 2: as you know, if you separate people into quartiles of

162
00:12:34,360 --> 00:12:42,439
Speaker 2: walking speed. That's fitness, and that's future life expectancy. That's function.

163
00:12:43,040 --> 00:12:46,840
Speaker 2: That's being able to run after your kids or grandkids,

164
00:12:47,920 --> 00:12:52,719
Speaker 2: make love to your partner, and you know, do a

165
00:12:52,760 --> 00:12:55,439
Speaker 2: full day of work or a full day of recreation.

166
00:12:56,120 --> 00:12:58,560
Speaker 2: Walking speed is life.

167
00:12:59,080 --> 00:13:04,320
Speaker 1: It's it's it's functional capacity, isn't it? And you know,

168
00:13:04,360 --> 00:13:08,480
Speaker 1: and it's also strongly related to VO two max, right,

169
00:13:08,840 --> 00:13:11,400
Speaker 1: which in the data is the strongest predictive of how

170
00:13:11,400 --> 00:13:14,000
Speaker 1: long you're going to live. Right, And you combine walking

171
00:13:14,040 --> 00:13:17,960
Speaker 1: speed with grip strength, Oh my god, you can forget

172
00:13:18,000 --> 00:13:21,839
Speaker 1: about all those other tests, not just the DNA methalations. Right,

173
00:13:22,520 --> 00:13:26,120
Speaker 1: those two combined are way more predictive of how someone's

174
00:13:26,120 --> 00:13:30,960
Speaker 1: going to live, even than diabetes, carniorder disease, all of that, if.

175
00:13:30,880 --> 00:13:34,600
Speaker 2: You would see right right, Yes, so.

176
00:13:34,240 --> 00:13:37,440
Speaker 1: Sorry, I just wanted to just before we move on

177
00:13:37,480 --> 00:13:40,560
Speaker 1: to this, I just wanted to quickly sidestep into the

178
00:13:40,679 --> 00:13:46,920
Speaker 1: DNA methalation clocks, which are again all over the internet

179
00:13:47,160 --> 00:13:50,960
Speaker 1: in terms of and papers reducing biologically do you know what?

180
00:13:51,080 --> 00:13:53,360
Speaker 1: And I've got quite interested in those, but do you

181
00:13:53,400 --> 00:13:57,360
Speaker 1: know what really put me off those Matt Chamberlin, who

182
00:13:57,440 --> 00:14:00,280
Speaker 1: I'm sure you're pretty aware of who's a you know,

183
00:14:01,240 --> 00:14:05,720
Speaker 1: a big researcher for thees in the intervention's testing programs.

184
00:14:05,920 --> 00:14:10,200
Speaker 1: He did and the four major ones that are out there,

185
00:14:10,360 --> 00:14:14,800
Speaker 1: GRIMMAGE and DNA, and I can't remember the other two.

186
00:14:14,880 --> 00:14:17,960
Speaker 1: But he did all four of them, and he ordered

187
00:14:18,000 --> 00:14:20,920
Speaker 1: two tests of each. He got them all delivered at

188
00:14:20,920 --> 00:14:23,920
Speaker 1: the same time. So he did eight tests, all one

189
00:14:23,960 --> 00:14:27,480
Speaker 1: after the other, sent them back in under different names.

190
00:14:27,720 --> 00:14:31,960
Speaker 1: Kit they came back he got eight different biological ages

191
00:14:32,600 --> 00:14:36,040
Speaker 1: and that's when I went, Wow, this stuff is nowhere

192
00:14:36,120 --> 00:14:38,000
Speaker 1: near ready in terms of.

193
00:14:38,960 --> 00:14:43,760
Speaker 2: It's even worse in the laboratory because somebody will do

194
00:14:45,120 --> 00:14:50,600
Speaker 2: some type of intervention on mice or maybe on people,

195
00:14:51,560 --> 00:14:57,840
Speaker 2: and then they can test multiple methylation age tests or

196
00:14:57,880 --> 00:15:01,840
Speaker 2: other type of age kits, and if they want to

197
00:15:02,080 --> 00:15:06,000
Speaker 2: show efficacy, they could basically choose the one that works.

198
00:15:06,840 --> 00:15:11,920
Speaker 2: It works, yes, yes, supports their priors, yes yes, yes,

199
00:15:12,480 --> 00:15:16,680
Speaker 2: but walking speed doesn't lie, just like hips don't lie, right.

200
00:15:17,000 --> 00:15:18,800
Speaker 1: Just like grip strength and VOTMX.

201
00:15:19,280 --> 00:15:24,040
Speaker 2: So back to perferal ry disease. Folks that are enrolled

202
00:15:24,280 --> 00:15:28,720
Speaker 2: in clinical trials of peripheral ry disease, you do a

203
00:15:29,000 --> 00:15:32,080
Speaker 2: I can't remember how long the studies typically go, maybe

204
00:15:32,120 --> 00:15:36,000
Speaker 2: thirteen weeks. Don't quote me on that. I'm going to

205
00:15:36,360 --> 00:15:41,000
Speaker 2: look that one up. But these folks are in decline. Yes,

206
00:15:41,120 --> 00:15:46,520
Speaker 2: so the placebo arm the walking speed is shorter, you know,

207
00:15:46,720 --> 00:15:48,240
Speaker 2: in the length of the trial.

208
00:15:48,280 --> 00:15:52,000
Speaker 1: Because they're naturally declining with the edge. They're older people alone.

209
00:15:52,640 --> 00:15:59,400
Speaker 2: So McDermott at Northwestern was in She does a lot

210
00:15:59,440 --> 00:16:02,960
Speaker 2: of things in collaborations with different groups that have different

211
00:16:03,440 --> 00:16:07,880
Speaker 2: you know, interests, And the group that she was interested

212
00:16:07,960 --> 00:16:12,400
Speaker 2: in that she collaborated with a year or two ago

213
00:16:12,760 --> 00:16:17,440
Speaker 2: was at University of Florida. They were interested in NAD Okay,

214
00:16:18,120 --> 00:16:24,720
Speaker 2: so they wanted nicotinamide rib aside as the intervention. They

215
00:16:24,720 --> 00:16:30,720
Speaker 2: were funded by the National Institutes on Aging, which had

216
00:16:30,760 --> 00:16:35,800
Speaker 2: been tremendously influenced by this rosveratrol stuff. Yes, they said,

217
00:16:35,840 --> 00:16:39,160
Speaker 2: we're going to give you the money, but you can't

218
00:16:39,240 --> 00:16:44,720
Speaker 2: do two doses of n R against placebo. You have

219
00:16:44,840 --> 00:16:50,120
Speaker 2: to do nicotinamide ribe aside plus or minus rose a veratrol.

220
00:16:50,720 --> 00:16:53,200
Speaker 2: Oh really, okay, let me tell you what the result was.

221
00:16:54,240 --> 00:17:02,400
Speaker 2: Nicotinamide ribe aside met the primary endpoint of increasing walking

222
00:17:02,440 --> 00:17:06,359
Speaker 2: speed with respect to placebo. They had a longer walking

223
00:17:06,400 --> 00:17:09,960
Speaker 2: speed than when they started. But more importantly, it's a

224
00:17:09,960 --> 00:17:14,760
Speaker 2: placebook control trial. So you look at the walking speed

225
00:17:15,080 --> 00:17:18,000
Speaker 2: at the end of the trial for placebo, which was shorter,

226
00:17:18,720 --> 00:17:20,879
Speaker 2: versus the walking speed at the end of the trial

227
00:17:20,880 --> 00:17:24,000
Speaker 2: with nicoten rid ribiside, which was longer, and it met

228
00:17:24,040 --> 00:17:31,160
Speaker 2: their primary endpoint. It scored positive nicotinamide ribiside plus rosveratrol.

229
00:17:31,280 --> 00:17:37,320
Speaker 2: Rosveratrol actually degraded the positive effect of NR mc dermott.

230
00:17:37,880 --> 00:17:42,960
Speaker 2: McDermott published this in Nature Communications. Fast forward to last week.

231
00:17:44,240 --> 00:17:48,520
Speaker 2: You and I are recording this in November. Today is

232
00:17:48,600 --> 00:17:55,600
Speaker 2: November tenth, and last week McDermott with a number of

233
00:17:55,640 --> 00:18:01,240
Speaker 2: other collaborators tested mcforman right because wants to test met

234
00:18:01,280 --> 00:18:03,840
Speaker 2: Foreman in age related conditions.

235
00:18:04,200 --> 00:18:11,040
Speaker 1: Can I guess fail, Yeah, that foreman. I put net

236
00:18:11,119 --> 00:18:15,920
Speaker 1: Foreman andres vitral in one of those. It's the old

237
00:18:15,960 --> 00:18:18,040
Speaker 1: azzie yeah nah, which.

238
00:18:17,880 --> 00:18:20,679
Speaker 2: Is well, no, met Foreman is a real drug.

239
00:18:20,880 --> 00:18:25,120
Speaker 3: I mean, so you know, if they have two diabetics,

240
00:18:25,720 --> 00:18:31,560
Speaker 3: you know, then maybe And I don't understand enough about

241
00:18:31,560 --> 00:18:35,320
Speaker 3: the mechanisms of action of met Foreman because there's so many.

242
00:18:36,720 --> 00:18:41,200
Speaker 2: But you know, personally, I'm not about to go out

243
00:18:41,240 --> 00:18:46,600
Speaker 2: and take a complex one inhibitor. You know something that

244
00:18:46,600 --> 00:18:50,879
Speaker 2: that you know in some ways impairs my chondral function

245
00:18:52,359 --> 00:18:57,800
Speaker 2: that has a role in lowering blood glucose because there's

246
00:18:57,880 --> 00:19:04,040
Speaker 2: a step or two in lukenagenesis that requires mitochondrial activities.

247
00:19:05,600 --> 00:19:12,080
Speaker 2: But basically, you know, met form bottom line is metform

248
00:19:12,160 --> 00:19:17,760
Speaker 2: and failed in perferal artery disease. And the same senior

249
00:19:17,800 --> 00:19:23,000
Speaker 2: author McDermott showed that nicotinride ribside worked. So they're doing

250
00:19:23,240 --> 00:19:26,000
Speaker 2: you know, they're planning a larger they're roll enrolling a

251
00:19:26,080 --> 00:19:29,240
Speaker 2: larger trial for NR and Purferle artery disease, and I

252
00:19:29,240 --> 00:19:31,600
Speaker 2: think that that could be it could be huge. So

253
00:19:31,640 --> 00:19:36,320
Speaker 2: we have eight positive results on anti inflammatory activity and

254
00:19:36,400 --> 00:19:39,400
Speaker 2: people we have Perferle artery disease, and there's a number

255
00:19:39,480 --> 00:19:42,200
Speaker 2: of other trials that are being done in the area

256
00:19:42,240 --> 00:19:46,840
Speaker 2: of neurodegeneration. Long COVID. We could talk about long COVID

257
00:19:46,920 --> 00:19:51,600
Speaker 2: because I think by the time you air this podcast,

258
00:19:52,200 --> 00:19:55,800
Speaker 2: there's going to be a long COVID publication.

259
00:19:57,000 --> 00:19:59,760
Speaker 1: Interesting before we jump into that, and I do want

260
00:19:59,800 --> 00:20:00,879
Speaker 1: one to jump into that.

261
00:20:01,600 --> 00:20:04,760
Speaker 4: I think it's really important charge for our listeners to

262
00:20:05,080 --> 00:20:13,359
Speaker 4: understand when proper scientists draw start to draw conclusions about

263
00:20:13,880 --> 00:20:17,679
Speaker 4: research about the efficacy of whatever intervention it is.

264
00:20:18,200 --> 00:20:22,080
Speaker 1: Now, you have mentioned things that maybe some listeners may

265
00:20:22,119 --> 00:20:26,879
Speaker 1: have not picked up on, but things like the laboratory

266
00:20:27,040 --> 00:20:32,280
Speaker 1: that's doing the trial and being a highly regarded laboratory

267
00:20:32,400 --> 00:20:35,280
Speaker 1: and not just some ship kickers.

268
00:20:35,320 --> 00:20:38,040
Speaker 2: Also, they have no investment in and R met Foreman.

269
00:20:38,840 --> 00:20:41,240
Speaker 2: This is they have a thirty year history and trying

270
00:20:41,280 --> 00:20:43,160
Speaker 2: to help people would prefer our disease.

271
00:20:43,359 --> 00:20:47,600
Speaker 1: Yes, you know, no industry links, right, which is another

272
00:20:47,640 --> 00:20:48,080
Speaker 1: big one.

273
00:20:48,240 --> 00:20:51,000
Speaker 2: I don't know about every single author you know in

274
00:20:52,160 --> 00:20:56,280
Speaker 2: both of those papers. I know I wasn't involved in them,

275
00:20:56,800 --> 00:21:00,520
Speaker 2: and that the senior authors are are at nor Western.

276
00:21:01,240 --> 00:21:05,480
Speaker 1: Yeah. And I think the other thing as well, charges

277
00:21:05,760 --> 00:21:11,719
Speaker 1: is that different labs doing similar things getting the same results.

278
00:21:12,080 --> 00:21:15,600
Speaker 1: That's when you start to set up and take notice,

279
00:21:15,800 --> 00:21:22,159
Speaker 1: right that we're then starting to get an accumulation of

280
00:21:22,720 --> 00:21:27,879
Speaker 1: good quality evidence as opposed to a lot of the

281
00:21:27,880 --> 00:21:30,560
Speaker 1: stuff that you see on the internet chided and with

282
00:21:30,720 --> 00:21:35,880
Speaker 1: some bloody influencer Harvard professor on there talking about why

283
00:21:35,920 --> 00:21:37,959
Speaker 1: he takes it and all of this stuff. Right, So

284
00:21:38,400 --> 00:21:42,879
Speaker 1: that's the difference between pseudo science marketing and real science.

285
00:21:42,920 --> 00:21:45,439
Speaker 1: So now that that's been established, I just want to

286
00:21:45,440 --> 00:21:48,639
Speaker 1: go back a little bit and explore an a D

287
00:21:48,880 --> 00:21:51,359
Speaker 1: plus because I mean, you were throwing out lots of

288
00:21:51,480 --> 00:21:56,960
Speaker 1: terms around metabolism, electron transport chain, just from a simplified

289
00:21:57,040 --> 00:21:59,399
Speaker 1: perspective for the listeners who may not be up on

290
00:21:59,440 --> 00:22:08,520
Speaker 1: their bow, biochemistry, just tell us high important nada's in.

291
00:22:08,359 --> 00:22:13,879
Speaker 2: The body, right, So, I mean, cells can't convert fuels

292
00:22:14,040 --> 00:22:19,280
Speaker 2: to energy without a transmitter of what are called high

293
00:22:19,359 --> 00:22:25,400
Speaker 2: energy electrons. And that's fundamentally what nad coenzymes do is

294
00:22:25,400 --> 00:22:32,440
Speaker 2: that they capture high energy electrons from food oxidation, from

295
00:22:32,560 --> 00:22:37,719
Speaker 2: burning our fuel. The amazing thing about biological systems is

296
00:22:37,760 --> 00:22:43,760
Speaker 2: that the energy can be extracted without lighting a match

297
00:22:44,160 --> 00:22:49,240
Speaker 2: and allowing the high energy electrons to go up in smoke.

298
00:22:49,800 --> 00:22:55,440
Speaker 2: They're basically the high energy electrons are carried on nad

299
00:22:55,600 --> 00:23:00,720
Speaker 2: coenzymes and then transmitted to other enzymatic processes that need

300
00:23:00,800 --> 00:23:06,679
Speaker 2: those electrons. So in order to make lipids and in

301
00:23:06,800 --> 00:23:13,560
Speaker 2: order to convert RNA nucleotides to DNA nucleotides, in order

302
00:23:13,560 --> 00:23:18,479
Speaker 2: to make DNA, you need two pairs of electrons. In

303
00:23:18,560 --> 00:23:22,000
Speaker 2: order to make the carbon carbon bonds and extend a

304
00:23:22,359 --> 00:23:26,400
Speaker 2: carbon chain to make lipids, or in order to convert

305
00:23:26,440 --> 00:23:30,879
Speaker 2: a what's called a ribonucleotide to a deoxy ribon nucleotide,

306
00:23:31,000 --> 00:23:35,720
Speaker 2: you need these these electrons and those are carried on NAD.

307
00:23:36,160 --> 00:23:42,440
Speaker 2: So under conditions where the NAD system comes under attack,

308
00:23:44,720 --> 00:23:49,159
Speaker 2: the mitochondria kind of hangs on to its NAD coenzymes

309
00:23:49,560 --> 00:23:53,440
Speaker 2: longer than the than the cytosol does, but ultimately all

310
00:23:53,480 --> 00:23:58,200
Speaker 2: of metabolism can become compromised. And then because NAD is

311
00:23:58,240 --> 00:24:04,480
Speaker 2: also used to repair DNA and to detoxify free radical species,

312
00:24:05,160 --> 00:24:10,359
Speaker 2: it's really central, you know, to repair and to you know,

313
00:24:10,520 --> 00:24:14,119
Speaker 2: maintenance of cellular health. And and now we can measure

314
00:24:14,240 --> 00:24:19,760
Speaker 2: its effect on human health because you know, in chronic

315
00:24:19,840 --> 00:24:25,679
Speaker 2: inflammatory conditions you have these things like IL ten and

316
00:24:25,760 --> 00:24:31,119
Speaker 2: ASLE six that are that are elevated and and initially

317
00:24:32,440 --> 00:24:36,720
Speaker 2: in response to an infection, you get an inflammatory response

318
00:24:36,760 --> 00:24:42,040
Speaker 2: that's supposed to help your tissues heal. But in older people,

319
00:24:42,080 --> 00:24:46,199
Speaker 2: as you know, they circulate these inflammatory markers all the

320
00:24:46,280 --> 00:24:55,400
Speaker 2: time and it's kind of contraindicated. So by suppressing the

321
00:24:55,400 --> 00:25:01,720
Speaker 2: the hyperactive inflammatory system and R can base get cells

322
00:25:01,720 --> 00:25:06,440
Speaker 2: and tissues to focus more on productive healing rather than

323
00:25:07,040 --> 00:25:10,440
Speaker 2: just spewing out in plammatory markers.

324
00:25:10,480 --> 00:25:15,280
Speaker 1: And so basically our rough layman's translation of all of

325
00:25:15,320 --> 00:25:18,600
Speaker 1: that charge is that if you don't have a NAD,

326
00:25:19,600 --> 00:25:23,119
Speaker 1: magic shit doesn't happen in your sales to allow you

327
00:25:23,280 --> 00:25:24,280
Speaker 1: to still be alive.

328
00:25:24,640 --> 00:25:27,239
Speaker 2: Right, So it is, I mean, it is amazing what

329
00:25:27,280 --> 00:25:32,119
Speaker 2: biology does when we think, you know, let me show

330
00:25:32,160 --> 00:25:36,680
Speaker 2: mad respect to human longevity, okay, because you know, you

331
00:25:37,200 --> 00:25:41,840
Speaker 2: and I can probably both expect to live into our nineties,

332
00:25:43,880 --> 00:25:49,120
Speaker 2: you know, with some vigor, Okay, And that's just amazing

333
00:25:49,640 --> 00:25:54,200
Speaker 2: because if we live till ninety five and we could

334
00:25:54,240 --> 00:25:59,800
Speaker 2: reproduce when we were fifteen, that's eighty years of keeping

335
00:25:59,840 --> 00:26:05,879
Speaker 2: are stuff together. I mean, that's an amazing thing. Eight decades.

336
00:26:06,280 --> 00:26:10,879
Speaker 2: Yeahs reproductive, because the way that animals are built and

337
00:26:10,960 --> 00:26:20,480
Speaker 2: evolve is you get to reproductive capacity, Yeah, compete for mating, yes,

338
00:26:21,600 --> 00:26:25,920
Speaker 2: create some offspring, and then you're not that useful.

339
00:26:26,160 --> 00:26:30,560
Speaker 1: Now, that's right, And the major, the major driver of

340
00:26:30,600 --> 00:26:34,560
Speaker 1: your genome is not about you. It's about survival of

341
00:26:34,600 --> 00:26:35,800
Speaker 1: the species, isn't it so?

342
00:26:36,200 --> 00:26:36,320
Speaker 2: Right?

343
00:26:36,480 --> 00:26:40,919
Speaker 1: So basically you're talking about an eighty year upside after

344
00:26:41,080 --> 00:26:44,760
Speaker 1: we've actually done the job that our genome months.

345
00:26:44,800 --> 00:26:47,960
Speaker 2: The most West didn't reproduced when we were fifteen, but

346
00:26:50,160 --> 00:26:57,600
Speaker 2: we could have and and and and it is. It

347
00:26:57,640 --> 00:27:01,000
Speaker 2: is remark so because people ask these questions like when

348
00:27:01,040 --> 00:27:05,000
Speaker 2: does aging begin, Well, aging begins probably with fertilization of

349
00:27:05,040 --> 00:27:10,120
Speaker 2: the of yes, and aging is not the enemy, right

350
00:27:10,240 --> 00:27:14,680
Speaker 2: because if you didn't have a developmental program to age

351
00:27:14,800 --> 00:27:24,200
Speaker 2: from fertilization to you know, birth to growth and puberty,

352
00:27:24,440 --> 00:27:29,879
Speaker 2: you know, you wouldn't have been a functioning human. That

353
00:27:29,640 --> 00:27:33,679
Speaker 2: the part of aging that people have a problem with is,

354
00:27:34,359 --> 00:27:40,640
Speaker 2: you know, age related decline. You know, after you're beyond

355
00:27:40,800 --> 00:27:46,640
Speaker 2: reproductive capacity and you're finding that it's harder to you know,

356
00:27:46,760 --> 00:27:51,000
Speaker 2: maintain muscle mass and it's harder, but your brain is

357
00:27:51,040 --> 00:27:56,199
Speaker 2: probably still maturing if you're male, certainly until you're thirty

358
00:27:56,320 --> 00:28:01,960
Speaker 2: or you know, I'm sixty for now and still making

359
00:28:02,040 --> 00:28:05,480
Speaker 2: mistakes that I think I might be able to avoid.

360
00:28:05,600 --> 00:28:10,320
Speaker 2: So we'd like to be able to have productive maturation

361
00:28:10,560 --> 00:28:13,440
Speaker 2: for a long period of time. And what we're going

362
00:28:13,480 --> 00:28:17,720
Speaker 2: for is mastery, right and being able to take care

363
00:28:17,760 --> 00:28:22,520
Speaker 2: of yourself and others. And so humans are extremely good

364
00:28:22,560 --> 00:28:26,880
Speaker 2: at aging. Humans are better at aging than gorillas, which

365
00:28:26,920 --> 00:28:30,560
Speaker 2: you would not expect from our size because gorillas are

366
00:28:30,560 --> 00:28:36,080
Speaker 2: bigger than us. The general rule is bigger body, longer

367
00:28:36,119 --> 00:28:41,160
Speaker 2: life spiking, right, But humans live longer than gorillas. And

368
00:28:42,920 --> 00:28:50,320
Speaker 2: then women are even the biggest head scratcher because women

369
00:28:51,280 --> 00:28:56,200
Speaker 2: reach a menopause at an average age of fifty one,

370
00:28:56,520 --> 00:29:03,680
Speaker 2: so they're no longer reproductively viable, but in their sixth, seventh, eighth,

371
00:29:03,760 --> 00:29:09,200
Speaker 2: and ninth decade are actually healthier than men, right, and

372
00:29:09,320 --> 00:29:13,400
Speaker 2: have a better life expectancy than men post menopause, which

373
00:29:13,920 --> 00:29:18,800
Speaker 2: evolution can't explain other than to say that grandmothers are

374
00:29:18,880 --> 00:29:23,560
Speaker 2: really really important again for the survival of the species.

375
00:29:24,120 --> 00:29:25,160
Speaker 1: Yes that you.

376
00:29:25,040 --> 00:29:30,160
Speaker 2: Know human human you know children human babies and children

377
00:29:30,240 --> 00:29:36,200
Speaker 2: are pretty inept as as animal offspring go, right, Like

378
00:29:36,240 --> 00:29:41,520
Speaker 2: if you've seen videos of giraffes or horses being born,

379
00:29:41,000 --> 00:29:47,880
Speaker 2: and like watch for ten minutes for something remarkable to happen,

380
00:29:48,120 --> 00:29:51,640
Speaker 2: like as soon as it gets up and as belly

381
00:29:51,720 --> 00:29:54,800
Speaker 2: is not on the ground, it might still be dripping wet,

382
00:29:55,240 --> 00:30:01,920
Speaker 2: it's going to run. Yeah, that's just astonishing.

383
00:30:02,160 --> 00:30:07,040
Speaker 1: It takes us three years to do that, right, and

384
00:30:07,040 --> 00:30:10,680
Speaker 1: and probably the limit limiting factors that are brain size.

385
00:30:10,760 --> 00:30:13,880
Speaker 1: But now, as you were talking, about all of that

386
00:30:14,120 --> 00:30:19,040
Speaker 1: and talking about the nady and its central role in metabolism,

387
00:30:19,480 --> 00:30:22,800
Speaker 1: and straight away in my head, I'm going boom, boom boom,

388
00:30:22,840 --> 00:30:26,720
Speaker 1: I'm going hallmarks of aging. You know, some of my

389
00:30:26,760 --> 00:30:30,200
Speaker 1: listeners will be familiar with the nine hallmarks of aging

390
00:30:30,280 --> 00:30:33,080
Speaker 1: that then get upgraded to the twelve hallmarks of aging.

391
00:30:33,400 --> 00:30:36,960
Speaker 1: But straight away I'm going DNA rapair that's the hallmark

392
00:30:36,960 --> 00:30:42,760
Speaker 1: of aging. So inflammation that's another hallmark of aging. Stem Oh,

393
00:30:42,800 --> 00:30:46,240
Speaker 1: there you go. So I was going to say mitochondrict function.

394
00:30:46,720 --> 00:30:50,320
Speaker 1: Then you have stem cell meeting. So there's there's four already.

395
00:30:50,560 --> 00:30:52,720
Speaker 1: And you know if probably if we had the entire

396
00:30:52,760 --> 00:30:54,720
Speaker 1: list in front of us and went through it, there'd

397
00:30:54,720 --> 00:31:00,800
Speaker 1: probably be another view. So that really does emphasize its

398
00:31:00,840 --> 00:31:07,920
Speaker 1: importance in the aging process. Are in overall healthy, right,

399
00:31:08,280 --> 00:31:11,360
Speaker 1: And like you say, I don't think we're going to

400
00:31:11,400 --> 00:31:15,640
Speaker 1: get escape velocity, but what we can do is age better, right,

401
00:31:16,200 --> 00:31:18,920
Speaker 1: And I think that we're definitely on the custom.

402
00:31:19,400 --> 00:31:22,080
Speaker 2: So let's think about the challenges of living in twenty

403
00:31:22,160 --> 00:31:26,320
Speaker 2: twenty five, twenty twenty six, right, So long COVID right

404
00:31:26,480 --> 00:31:29,280
Speaker 2: is out there? Yes, you know, this is a real thing.

405
00:31:30,000 --> 00:31:34,640
Speaker 2: It's probably kind of heterogeneous. So what do you get

406
00:31:34,680 --> 00:31:37,520
Speaker 2: when you enroll people in a trial for long COVID?

407
00:31:37,840 --> 00:31:41,240
Speaker 2: Do they all have exactly the same disease? They all

408
00:31:41,280 --> 00:31:45,360
Speaker 2: have exactly the same presentation? Maybe not, but there's a

409
00:31:45,760 --> 00:31:50,960
Speaker 2: kind of positive result that's that's that's coming out now. Wow,

410
00:31:51,000 --> 00:31:56,040
Speaker 2: So let's not dump on on Harvard, you know, entirely

411
00:31:56,560 --> 00:32:03,120
Speaker 2: because the study was done at mass General Hospital, and

412
00:32:03,120 --> 00:32:07,920
Speaker 2: and and study material was provided by Niagen Biosciences. I

413
00:32:08,440 --> 00:32:11,040
Speaker 2: was a middle author of the paper. I'm a you know,

414
00:32:11,120 --> 00:32:15,600
Speaker 2: chief science advisor of Niagen. I don't work for Niagen,

415
00:32:15,800 --> 00:32:21,720
Speaker 2: but I do consult for them. And but this study

416
00:32:21,840 --> 00:32:27,200
Speaker 2: was done by really good clinical trialists. And you know,

417
00:32:27,320 --> 00:32:31,160
Speaker 2: of course, the gold standard result would be would be

418
00:32:31,280 --> 00:32:33,880
Speaker 2: the kind of thing that was just reported for perferal

419
00:32:34,040 --> 00:32:38,680
Speaker 2: artery disease, Right that you have a placebo group, and

420
00:32:38,800 --> 00:32:42,240
Speaker 2: you have the intervention group, and you have a pre

421
00:32:42,360 --> 00:32:46,080
Speaker 2: specified endpoint, which in the case of prefer artery disease

422
00:32:46,960 --> 00:32:51,560
Speaker 2: was the six minute walk test, and the intervention group,

423
00:32:51,600 --> 00:32:56,160
Speaker 2: the n R group, was demonstrably better right than the

424
00:32:56,160 --> 00:33:00,000
Speaker 2: placebo group. Now, but there's other things that you can

425
00:33:00,080 --> 00:33:05,480
Speaker 2: look for as well, particularly when the disease doesn't present

426
00:33:05,840 --> 00:33:09,480
Speaker 2: exactly the same in every person. Right, So you have

427
00:33:09,560 --> 00:33:16,680
Speaker 2: the beginning measurements of executive function, fatigue, sleep quality, depression,

428
00:33:17,360 --> 00:33:21,040
Speaker 2: and then you have the end of study measurements of

429
00:33:21,120 --> 00:33:25,760
Speaker 2: the same thing executive function, fatigue, sleep and depression, and

430
00:33:25,800 --> 00:33:29,040
Speaker 2: then you can see whether place EBO move the needle

431
00:33:30,160 --> 00:33:35,000
Speaker 2: or NR moved the needle in the same individuals. Right. So,

432
00:33:35,920 --> 00:33:41,400
Speaker 2: early days of clinical trials for long COVID didn't meet

433
00:33:41,440 --> 00:33:47,120
Speaker 2: the endpoint of placebo controlled results, again potentially because of

434
00:33:47,160 --> 00:33:51,600
Speaker 2: a lot of individual variability. But when you look at

435
00:33:52,000 --> 00:33:58,760
Speaker 2: times zero versus end of trial, the NR participants had

436
00:33:58,800 --> 00:34:05,560
Speaker 2: improvements in executive function, improvements in sleep quality, lower depressive scores,

437
00:34:06,120 --> 00:34:11,640
Speaker 2: and lower severity of fatigue, and the Paciba group did not. Wow,

438
00:34:11,800 --> 00:34:18,319
Speaker 2: So it's looking pretty promising. And I'm excited because we

439
00:34:18,400 --> 00:34:25,279
Speaker 2: have a safe, you know, clinically tested, patented, you know

440
00:34:26,880 --> 00:34:32,640
Speaker 2: supplement that is being conservatively you know, offered to the

441
00:34:33,080 --> 00:34:38,360
Speaker 2: public where the same exact material is available to medical

442
00:34:38,400 --> 00:34:42,560
Speaker 2: researchers in these clinical trials. Right, That's not the case

443
00:34:42,600 --> 00:34:48,080
Speaker 2: for NMN. Right, most of the men out there is

444
00:34:49,360 --> 00:34:53,520
Speaker 2: not doesn't meet the label claims, Like ninety percent of

445
00:34:53,600 --> 00:35:00,479
Speaker 2: the NMN stuff that is sold doesn't actually have men

446
00:35:00,520 --> 00:35:02,719
Speaker 2: in it or the amount of nmen that it says

447
00:35:02,760 --> 00:35:06,960
Speaker 2: of the label. Uh, the chemistry doesn't really make sense

448
00:35:07,080 --> 00:35:10,240
Speaker 2: to deliver n amen because it has to be converted

449
00:35:10,239 --> 00:35:10,680
Speaker 2: to n R.

450
00:35:10,880 --> 00:35:15,040
Speaker 1: But that was hard of the differences in in in

451
00:35:15,080 --> 00:35:18,520
Speaker 1: that and n R. So sorry, I just finished what

452
00:35:18,520 --> 00:35:19,840
Speaker 1: you said, and Net's come back to that.

453
00:35:20,640 --> 00:35:23,359
Speaker 2: Well, I mean the company, there's a company that is

454
00:35:24,000 --> 00:35:26,520
Speaker 2: testing and a man is a drug, and that's good,

455
00:35:26,600 --> 00:35:29,480
Speaker 2: that's I'm glad that they're they're doing that, and I'm

456
00:35:29,480 --> 00:35:35,759
Speaker 2: sure that their material is safety tested and you know,

457
00:35:35,840 --> 00:35:38,160
Speaker 2: shown to be safe and humans. In fact, I've seen

458
00:35:38,280 --> 00:35:41,799
Speaker 2: some evidence of that in the in the literature. But

459
00:35:41,960 --> 00:35:47,000
Speaker 2: when when consumers go online to get an amen supplement,

460
00:35:47,120 --> 00:35:51,840
Speaker 2: there's no real telling what they're getting. On the other hand,

461
00:35:53,360 --> 00:35:58,960
Speaker 2: the these eight randomized clinical trials of showing anti inflammatory activity,

462
00:35:59,360 --> 00:36:03,520
Speaker 2: the positive clical trials showing peripheral artery disease improvement and

463
00:36:03,960 --> 00:36:07,800
Speaker 2: walking speed, and the newly released trial of long COVID

464
00:36:08,400 --> 00:36:11,600
Speaker 2: where within group, if you took an R you have

465
00:36:11,640 --> 00:36:17,000
Speaker 2: improvements in executive function, lower fatigue, better sleep quality, lower depression.

466
00:36:17,480 --> 00:36:20,920
Speaker 2: That's done with niagen okay, which is the same material

467
00:36:21,040 --> 00:36:24,319
Speaker 2: that consumers can get. Now, clinical trials are usually done

468
00:36:24,360 --> 00:36:29,040
Speaker 2: at like a gram okay, pa, Right, so consumer doses

469
00:36:29,160 --> 00:36:32,839
Speaker 2: might be three hundred milligrams, but people take you know,

470
00:36:33,000 --> 00:36:37,240
Speaker 2: three tablets and three capsules and they're at a clinical level.

471
00:36:37,960 --> 00:36:41,920
Speaker 1: And now that what you just said, I don't. I

472
00:36:42,000 --> 00:36:44,240
Speaker 1: want to make sure that our listeners understand the importance

473
00:36:44,239 --> 00:36:48,520
Speaker 1: of that, and I want to explore why it. So basically,

474
00:36:48,600 --> 00:36:51,520
Speaker 1: what you're saying is the animeen that they'll they'll use

475
00:36:51,560 --> 00:36:54,879
Speaker 1: in clinical trials, and even there's a question mark around

476
00:36:54,880 --> 00:36:59,160
Speaker 1: the metabolism of that, but that that that stuff is

477
00:36:59,200 --> 00:37:01,799
Speaker 1: not the same is a lot of the stuff that

478
00:37:01,880 --> 00:37:02,880
Speaker 1: you will buy.

479
00:37:04,239 --> 00:37:08,640
Speaker 2: It can't be the same because because there there's a

480
00:37:08,719 --> 00:37:15,680
Speaker 2: company that has a patent on the crystal form of

481
00:37:15,920 --> 00:37:20,400
Speaker 2: NMN that is they company?

482
00:37:20,840 --> 00:37:21,920
Speaker 1: Is that company?

483
00:37:22,120 --> 00:37:25,200
Speaker 2: Is that if it's in measure measure bio attack. Yeah,

484
00:37:26,320 --> 00:37:34,239
Speaker 2: and so well, you know, I think that it's good

485
00:37:34,480 --> 00:37:39,239
Speaker 2: that they're doing you know, careful clinical testing of a

486
00:37:39,760 --> 00:37:46,719
Speaker 2: pure beta and AMN. But the problem is that if

487
00:37:46,719 --> 00:37:50,760
Speaker 2: people are trying to get that same material, they can't

488
00:37:51,719 --> 00:37:56,520
Speaker 2: because when when a company decides to do a drug trial,

489
00:37:58,400 --> 00:38:03,240
Speaker 2: then they're not supposed to release that material as a supplement.

490
00:38:04,320 --> 00:38:07,239
Speaker 2: There have been a number of FDA rulings on this,

491
00:38:07,480 --> 00:38:09,759
Speaker 2: but in the in the case of the way Niagen

492
00:38:10,560 --> 00:38:14,960
Speaker 2: was introduced, the company then called chromot X now called

493
00:38:15,040 --> 00:38:23,160
Speaker 2: Nigen Bioscience first got FDA notifications that this is a

494
00:38:23,280 --> 00:38:26,480
Speaker 2: new dietary ingredient and generally regardless safe it could be

495
00:38:26,560 --> 00:38:30,839
Speaker 2: sold as in a food or supplement that means over

496
00:38:30,880 --> 00:38:36,240
Speaker 2: the counter, and then subsequently that material can be tested

497
00:38:36,840 --> 00:38:41,839
Speaker 2: as a drug. OK, But generally the ruling is it's

498
00:38:41,920 --> 00:38:47,040
Speaker 2: called the Dshay law d s h e A. The

499
00:38:47,120 --> 00:38:51,720
Speaker 2: Dshay Law says that if something is initially being tested

500
00:38:51,760 --> 00:38:54,560
Speaker 2: as a drug, you can't just go out and buy

501
00:38:54,640 --> 00:38:58,239
Speaker 2: it because that would basically it's you don't know that

502
00:38:58,360 --> 00:39:01,400
Speaker 2: it's safe. Right. You can't go out and buy things

503
00:39:01,480 --> 00:39:06,040
Speaker 2: that fail in clinical trials due to safety or loss

504
00:39:06,040 --> 00:39:08,759
Speaker 2: about non efficacy.

505
00:39:09,440 --> 00:39:14,239
Speaker 1: So touchards the other brands of n R that are

506
00:39:14,560 --> 00:39:17,880
Speaker 1: so how does an individual because there's a lot of

507
00:39:18,000 --> 00:39:24,440
Speaker 1: grandfathering of research, right, So one particular supplement that maybe

508
00:39:25,760 --> 00:39:28,160
Speaker 1: it may be a herb that's picked at a particular

509
00:39:28,280 --> 00:39:31,480
Speaker 1: time of year in a particular place and it has

510
00:39:32,960 --> 00:39:36,279
Speaker 1: done a randomized control trial and has efficacy. And then

511
00:39:36,400 --> 00:39:41,520
Speaker 1: you'll find other supplement companies with similar things, but turns

512
00:39:41,600 --> 00:39:44,560
Speaker 1: out that their herb is growing in a different place

513
00:39:44,680 --> 00:39:47,160
Speaker 1: and it has different qualities, and it's picked at a

514
00:39:47,239 --> 00:39:50,759
Speaker 1: different time of year and it's not the same. So

515
00:39:51,920 --> 00:39:56,760
Speaker 1: is this the case with n R with the trials

516
00:39:56,920 --> 00:40:00,000
Speaker 1: it's all an ar that's out there pretty much.

517
00:40:00,200 --> 00:40:03,440
Speaker 2: Is it all Nigen, No, it's probably not all Niagen.

518
00:40:05,080 --> 00:40:10,719
Speaker 2: There are a couple of other companies that actually used

519
00:40:10,719 --> 00:40:15,440
Speaker 2: to buy Niagen from chromon x slash Nigen Bioscience and

520
00:40:15,640 --> 00:40:23,600
Speaker 2: then went their own way, and you know, are selling

521
00:40:24,120 --> 00:40:26,719
Speaker 2: stuff that I can't really vouch for. I mean, I

522
00:40:26,840 --> 00:40:30,880
Speaker 2: haven't seen the safety data behind it. They certainly don't

523
00:40:31,360 --> 00:40:36,600
Speaker 2: have the safety dossier that that Nigen has. They're not

524
00:40:36,960 --> 00:40:43,480
Speaker 2: used in very many clinical trials, if at all. And

525
00:40:44,880 --> 00:40:49,520
Speaker 2: so the Nigen Blue bottle is kind of the safety

526
00:40:49,640 --> 00:40:52,719
Speaker 2: tested way to go if someone wants to test to

527
00:40:52,760 --> 00:40:56,759
Speaker 2: see whether you know, this has anti inflammatory activity for them.

528
00:40:56,960 --> 00:41:00,520
Speaker 1: And this is the key thing for individi Jels is

529
00:41:00,560 --> 00:41:02,880
Speaker 1: that if you're going to take a supplement because you

530
00:41:03,000 --> 00:41:07,200
Speaker 1: think it's it's having an impact and you've seen studies

531
00:41:07,239 --> 00:41:10,640
Speaker 1: published on it. You want to make sure if you

532
00:41:10,800 --> 00:41:14,200
Speaker 1: possibly can, that you're getting the exact supplement that was

533
00:41:14,280 --> 00:41:18,240
Speaker 1: used in the clinical trial, because others can be completely different.

534
00:41:18,239 --> 00:41:21,960
Speaker 1: I think that's something that a lot of people don't understand.

535
00:41:22,040 --> 00:41:25,520
Speaker 1: A lot of lay people don't understand, like the Amiga

536
00:41:25,560 --> 00:41:28,759
Speaker 1: three fatty acids that you can buy in chemist Warehouse,

537
00:41:28,840 --> 00:41:32,279
Speaker 1: which is a big, massive chain over here that does

538
00:41:32,320 --> 00:41:34,440
Speaker 1: a lot of cheap stuff, like like a lot of

539
00:41:34,520 --> 00:41:37,759
Speaker 1: that can be rancid shit, and it's very different to

540
00:41:37,840 --> 00:41:39,920
Speaker 1: some of the Amiga three fatty acids that are used

541
00:41:39,960 --> 00:41:42,960
Speaker 1: in clinical trials. I know which one I want, right,

542
00:41:43,960 --> 00:41:48,440
Speaker 1: That's really important I think for for people to understand. So,

543
00:41:49,840 --> 00:41:55,600
Speaker 1: I mean we've we've talked about that that clinical clinically proven,

544
00:41:55,880 --> 00:42:01,240
Speaker 1: and that that difference from if we go back again

545
00:42:01,360 --> 00:42:06,760
Speaker 1: and talk about nad plus, so the methods of getting

546
00:42:06,800 --> 00:42:12,360
Speaker 1: in so there's a lot of intravenous infusions of nad plus.

547
00:42:12,800 --> 00:42:17,160
Speaker 1: My understanding is that when you infuse nad plus, it's

548
00:42:17,200 --> 00:42:20,120
Speaker 1: got to go to the liver and then it's converted.

549
00:42:20,440 --> 00:42:23,040
Speaker 1: I can't remember whether it's an or whatever. It's converted

550
00:42:23,120 --> 00:42:23,640
Speaker 1: in the liver.

551
00:42:24,280 --> 00:42:30,719
Speaker 2: It's actually even worse than that. So it causes a

552
00:42:30,840 --> 00:42:37,000
Speaker 2: painful inflammatory reaction when it's when it's given by IV,

553
00:42:37,960 --> 00:42:42,840
Speaker 2: because the body thinks that there's some infection somewhere and

554
00:42:42,960 --> 00:42:50,319
Speaker 2: some cells are busted open. You don't normally circulate high

555
00:42:50,480 --> 00:42:56,280
Speaker 2: levels of NAD or ATP, or you don't generally circulate

556
00:42:57,040 --> 00:43:02,600
Speaker 2: mitochondria or chromosomal DNA. All of those things in circulation

557
00:43:02,920 --> 00:43:07,120
Speaker 2: can cause an inflammatory reaction. So NED is actually breaking

558
00:43:07,239 --> 00:43:11,319
Speaker 2: down in the bloodstream to NR, and then as NR

559
00:43:11,400 --> 00:43:12,560
Speaker 2: it can get into cells.

560
00:43:13,680 --> 00:43:19,279
Speaker 1: So it's a really expensive way and painful way of

561
00:43:19,440 --> 00:43:19,960
Speaker 1: getting some.

562
00:43:20,360 --> 00:43:23,759
Speaker 2: N R right and which you can get orally and

563
00:43:23,920 --> 00:43:28,640
Speaker 2: for which there's now hundreds of registered clinical trials attesting

564
00:43:28,719 --> 00:43:33,400
Speaker 2: its oral efficacy, including you know, ten eleven twelve trials

565
00:43:33,440 --> 00:43:37,000
Speaker 2: that we talked about that that are positive that said,

566
00:43:37,560 --> 00:43:41,680
Speaker 2: there are people that have sworn by the effects of

567
00:43:42,040 --> 00:43:49,520
Speaker 2: intravenous NAD, and so Niagen developed something called nigen plus,

568
00:43:50,239 --> 00:43:54,800
Speaker 2: which is a pharmaceutical grade n R that can be

569
00:43:54,960 --> 00:43:59,920
Speaker 2: delivered IV. And so it turns out it's three or

570
00:44:00,080 --> 00:44:04,640
Speaker 2: four times as fast because it can basically go in

571
00:44:05,160 --> 00:44:11,000
Speaker 2: without you know, without a painful reaction. There's not a

572
00:44:11,200 --> 00:44:16,919
Speaker 2: huge amount of scientific literature on it, other than there's

573
00:44:17,000 --> 00:44:21,320
Speaker 2: an initial report I think on the med Archives that

574
00:44:21,680 --> 00:44:27,000
Speaker 2: that shows that it did increase volunteers blood na D.

575
00:44:27,200 --> 00:44:32,560
Speaker 2: That's not too surprising that it was more rapidly administered

576
00:44:32,800 --> 00:44:37,720
Speaker 2: than intravenous na D. And so the good thing about

577
00:44:37,760 --> 00:44:41,480
Speaker 2: it is that it's available for use, it's available for

578
00:44:41,640 --> 00:44:46,120
Speaker 2: clinical testing. Now there's a lot of interest in its

579
00:44:46,239 --> 00:44:52,680
Speaker 2: potential activity as something that could curve cravings for opiates,

580
00:44:54,640 --> 00:44:58,680
Speaker 2: like a black market, gray market use of intravenous n

581
00:44:58,719 --> 00:45:03,480
Speaker 2: a D in drug recovery clinics, this stuff.

582
00:45:03,239 --> 00:45:07,839
Speaker 1: Like this, Wow, that's that's that's fascinating stuff. And very

583
00:45:07,960 --> 00:45:11,239
Speaker 1: quickly because I need to go to the airport, which

584
00:45:11,320 --> 00:45:14,840
Speaker 1: is very annoying because I'm loving this conversation. Talk about

585
00:45:15,840 --> 00:45:20,279
Speaker 1: its role in neuro degenda to the diseases, right, and

586
00:45:20,960 --> 00:45:23,680
Speaker 1: do you know of any clinical trials currently being done

587
00:45:23,760 --> 00:45:27,359
Speaker 1: looking at NAD plus or precursors or yes.

588
00:45:28,120 --> 00:45:34,799
Speaker 2: So there's a large trial in Norway on Parkinson's. There's

589
00:45:34,840 --> 00:45:38,879
Speaker 2: some trials in the US on my cognitive impairment. Most

590
00:45:38,920 --> 00:45:42,880
Speaker 2: of the people probably have early Alzheimer's that are enrolled

591
00:45:43,000 --> 00:45:46,320
Speaker 2: in those trials, and we're going to get the the

592
00:45:46,560 --> 00:45:54,359
Speaker 2: The trials from the early phase Parkinson's were promising enough

593
00:45:54,640 --> 00:46:00,520
Speaker 2: that the Norwegian government gave everybody niagen at the end

594
00:46:00,560 --> 00:46:02,800
Speaker 2: of the trial, so the folks that were on placebo

595
00:46:03,320 --> 00:46:06,960
Speaker 2: were able to get nigen because there appeared to be

596
00:46:07,560 --> 00:46:11,480
Speaker 2: improvements in cerebral blood flow. We know some of the

597
00:46:11,640 --> 00:46:17,239
Speaker 2: mechanisms by which NAD comes under attack in neurons. Ironically,

598
00:46:17,560 --> 00:46:24,080
Speaker 2: NMM accumulation in neurons is one of the bad actors,

599
00:46:24,760 --> 00:46:28,880
Speaker 2: and NMN turns on an enzyme called sarm one, and

600
00:46:28,960 --> 00:46:34,239
Speaker 2: then sarm one degrades NAD into cyclic adp ribos, which

601
00:46:34,719 --> 00:46:42,480
Speaker 2: mobilizes calcium and activates calpains and leads to neurodegenerative you know, collapse.

602
00:46:43,239 --> 00:46:49,719
Speaker 2: So NR has some strong potential in neuroprotection. And but

603
00:46:49,920 --> 00:46:53,200
Speaker 2: the you know, the clinical trials are the biggest clinical

604
00:46:53,280 --> 00:46:58,400
Speaker 2: trial is just being completed now in Norway.

605
00:46:59,000 --> 00:47:01,919
Speaker 1: Wow. That that is fascinating stuff. And so I'll watch

606
00:47:02,080 --> 00:47:06,080
Speaker 1: this space on that because you know the theory. I'm

607
00:47:06,120 --> 00:47:08,120
Speaker 1: sure you can talk about the theory all day long.

608
00:47:08,440 --> 00:47:11,640
Speaker 1: NAD plus is very important in the human brain as well,

609
00:47:12,840 --> 00:47:18,680
Speaker 1: and when it drops, bad shit happens, right, which I

610
00:47:18,760 --> 00:47:22,600
Speaker 1: think you've done a very good job charge of educating

611
00:47:22,719 --> 00:47:27,439
Speaker 1: our listeners both on the importance of NAD in terms

612
00:47:27,480 --> 00:47:32,719
Speaker 1: of metabolism as a as A as a A basically

613
00:47:32,880 --> 00:47:36,960
Speaker 1: a key driver of metabolism. But I think what has

614
00:47:37,040 --> 00:47:41,640
Speaker 1: also been great is helping people to understand the research

615
00:47:42,239 --> 00:47:44,360
Speaker 1: and what to look out for, not just with with

616
00:47:44,640 --> 00:47:48,439
Speaker 1: this particular supplement, but with any supplement. I think that's

617
00:47:48,480 --> 00:47:51,640
Speaker 1: been gold for the listeners to really understand that from

618
00:47:51,719 --> 00:47:56,640
Speaker 1: a somebody who's at the coalface doing research and we.

619
00:47:56,800 --> 00:48:02,120
Speaker 2: Want to over deliver and underpromise. And it was safety

620
00:48:02,239 --> 00:48:07,439
Speaker 2: first from the from the earliest days of nicotina white

621
00:48:07,480 --> 00:48:12,640
Speaker 2: ribside testing by Nigen Bioscience, And you know, at this

622
00:48:12,760 --> 00:48:15,640
Speaker 2: point there's a clinical track record and a safety track

623
00:48:15,760 --> 00:48:20,279
Speaker 2: record that I think that consumers can be confident in.

624
00:48:21,280 --> 00:48:26,120
Speaker 1: And and I have not got enough confidence that it's

625
00:48:26,600 --> 00:48:30,400
Speaker 1: buying onto my supplement lists. There's not many people who

626
00:48:30,480 --> 00:48:32,800
Speaker 1: can do that, who can sway me from sitting on

627
00:48:32,920 --> 00:48:36,680
Speaker 1: the fence to I mean, but I A mean, so

628
00:48:38,080 --> 00:48:40,000
Speaker 1: thank you very much. This has been awesome pleasure