Mitochondrial myopathy patients have NAD+ deficiency. Can Niacin, an NAD+ precursor help restore muscle strength and what impact does it have on healthy patients.
Hello and welcome to the shaky science show where in this video i’m going to discuss some recent data i’ve come from a human troll whereby they had participants take niacin for four to ten months to see if it could help treat patients with mitochondrial myopathy so i’ll discuss what all of these different terms mean and discussed their data and say this data was
Recently published in the cell metabolism paper that came out just the other day and is titled niacin kills systemic nad+ deficiency and improves muscle performance and adult onset mitochondrial myopathy say before i go into the results that they saw and some of the side effects of the study i’ll just explain what some of these terms mean so if i say let’s talk
About niacin because i’ve never spoken about it on this channel in any detail before so niacin is also referred to as vitamin b3 or nicotinic acid and it can be found lots of different food types such as meats fish legumes and seeds all nicing can be taken as supplements so nice and it’s best known as being a precursor to nad nicotinamide adenine dinucleotide and
They spoke about the metabolism of nad+ before in this channel and look how complicated it is but the sun was just gonna focus on the reads of niacin into nad class so the current mechanism linking niacin to nad plus formation is the priests handler pathway sir if i said that wrong and is named after the founders of the pathway and impose firstly nice and conversion
Into nicotinic acid mono nucleotides and then into nicotinic acid dinucleotide and then nad plus and so why do we care so much about nad plus well it’s one of the most abundant molecules in the body and is a really important cofactor for two major functions one of which is acting as a redox coenzyme and the other is acting as a substrate for nad requiring enzymes so
When this clinical trial they were using niacin to see if it has an impact on alleviating the symptoms of mitochondrial myopathy so why did they focus on a mitochondrial disease well the mitochondria is an organelle in the cell that performs every bit respiration and is actually a key regulator of the nad+ to the reduced form of nad+ nadh ratio so the mitochondrial
Disease that they focused on was mitochondrial myopathy and so this disease is characterized by a progressive weakness of eye muscles but also in general you see decline in wasty muscle weakness and fatigue ability and the major cause of this disease seen in adults is to see the accumulation of mutations in the dna that’s found in the mitochondria yes that’s right
You don’t only have dna in the nucleus and so these mutations are often deletions and so the push towards the human clinical trials here is due to the positive benefits they’ve already seen in mouse studies so by increasing the nad+ levels and mouse models of mitochondrial myopathy they saw an improvement and my total dysfunction and increase muscle strength and
So in this study they wanted to see what would happen if they treated human patients live nice and to try and increase the nad+ levels and so the setup of this clinical trial was between four and ten months for the patients and the controls and they increased the dose throughout the time as i written up here and say for the patients they did it for ten months and
The controls only for four months and the patients there was five of them there was one male and four females aged between 17 and 70 and for the controls they were age and sex matched and they were healthy so the first thing they needed to check was whether or not having nice and actually increased the nad+ levels because that was the main rationale behind their
Methods so firstly they looked at the nad+ levels in the muscle tissue and for this a tips and biopsy samples and so in the patients at four months in ten months they saw an increase in the muscle nad+ levels at one point three folds and a two point three fold increase and by ten months has actually matched the healthy control which they didn’t see an increase
Throughout the study even by taking niacin so besides looking at the muscle nad+ levels they also looked at the blood nad+ levels and they saw an increase in both the controls and the patients this time with a 7.1 fold increased by four months in the patients and a 5.7 fold increase in the controls and so obviously that’s proved that nice and worked at increasingly
Nad+ levels but the other question of the study is whether or not actually helps with the symptoms of mitochondrial myopathy but i think it’s a key thing to point out here that this was from looking at the bloods and 80-plus levels and this is potentially good as a diagnostic because the energyplus levels were lower in the mitochondrial myopathy patients than the
Controls to begin with in the study so it could be a good diagnostic for people with the condition and it’s a good way to track the effects of niacin throughout the study so so far they’ve proved that niacin is a powerful nad+ booster in humans both in healthy patient controls and patients but doesn’t help with the symptoms so to do this one of the things they
Looked at is whether or not they could restore muscle strength so one thing i haven’t actually mentioned yet which might just be of interest is why yuuji see a decrease in muscle strength when you have these mutations and the mitochondria and that’s mainly because the muscles such an energetic tissue and so it’s vulnerable to defects in the mitochondrial metabolism
Anyway back to the results so they saw increase in some of the muscles such as they have to run a muscle the back muscle short muscles and knee although these were to varying effects but unfortunately they didn’t see an improvement in the ocular muscles which they think is g’s the fact that this is one of the first muscles to become defective during mitochondrial
Myopathy so what are they see in the healthy controls well they also saw some slight increase in shoulder strength and the extension despite the fact that the nad+ levels in the muscle didn’t actually increase so what other effects that they see so interestingly they saw a decrease in the patient to pasok and fiscal fat otherwise referred to as the unhealthy fats
And they think that this could be due to the fact that from the improvements and mitochondrial performance they see increased oxidative phosphorylation which is aerobic respiration which could explain the increased metabolism and use of the fats there wasn’t a corresponding reduction in this unhealthy fat in the controls although they did see a whole-body reduction
In the fat percentage and in terms of the mitochondria itself and the patients whilst they saw an improvement they didn’t actually see any changes in the structure of the mitochondria or any change in the deletion load so besides these positive effects that they saw there were also some side effects reported and one of which is a reduction in hemoglobin which
I’ll come back to in just a minute so side effects seen in all of the patients included hot flushes and a tingling tingling cycling fear tingling sensation of extremities when they were taking more than 500 milligrams per day of nisan but as i said they also saw a reduction in hemoglobin which is the oxygen carrying compound that’s found in red blood cells that
Delivers oxygen around your body and they also saw a decrease in the red blood cell number so this is important to consider for the longevity of these studies and they also saw own gastrointestinal irritation such that two controls actually dropped out and then other side effects reported included skin drying and flatulence lovely so what can we actually take away
From these results so far well this study very much shows that niacin is effective at increasing the nad+ levels and the benefits that basal with the mitochondrial myopathy patients is thought to be by a metabolic bypass because they see these improvements in the metabolic functions without seeing improvements in the dna deletion of the mitochondrial dna but the
Problem is this is only there was only five patients they need to do it in a larger trial size i also try and see what the optimal dose is to try and minimize these side effects but i think overall this has been exciting study so far obviously it’s been done in patience and if you go into the clinical trial website which i’ll link in a description you can see more
Detail about the different measurements that they took so hopefully this was useful and as always thanks for listening
Transcribed from video
Niacin supplementation human clinical trial; mitochondrial myopathy & healthy controls By The Sheekey Science Show