It felt like I’d swallowed a stick of dynamite.
I tried to lay as still as possible. It felt like I’d swallowed a stick of dynamite that was slowly detonating. Any movement at all would send what seemed like waves of molten lava cascading inside me. As the burning sensations slowly eased, though, I felt an unusual state of clarity and calmness. My rushing mind and brain fog were gone. I was at peace.
That was my introduction to niacin (vitamin B3) – at the 500 mg level, no less – something I would not recommend as a starter dose. Over the past five years, I’ve used niacin intermittently and the effects have varied. Sometimes it does nothing at all. Other times, though, it produces 30 minutes or more of astounding calmness and clarity.
I have the idea that niacin’s flushing action – which leaves you with a burning sensation and your skin reddened for a period of time – may be needed for me to have positive effects but am not sure. Sometimes the flush occurs quickly; other times it can pop up unexpectedly half an hour or more later.
Something is definitely going on. I rarely respond so quickly and well to anything. I had never heard of niacin being used in chronic fatigue syndrome (ME/CFS) or fibromyalgia (FM) until I learned that Dr. Kerr in Toronto recommended it for some of her ME/CFS patients – presumably for its detoxification purposes.
Niacin, though, is a fascinating compound that intersects with several issues found in ME/CFS. The niacin blog is part 6 in a series of possible mitochondrial enhancers for ME/CFS, FM, and long COVID.
The Mitochondrial Enhancers for Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia and Long COVID Series
- Pt. I: D-Ribose, CoQ10 and PQQ
- Pt. II: L-carnitine and Acetylcarnitine
- Pt. III: Magnesium
- Pt. IV: N-acetyl cysteine (NAC)
- Pt. V: Oxaloacetate
- Pt. VI: Niacin, Nicotinamide, and Nicotinamide riboside
Electron Transfer Maestros
Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form, NADP, are electron transfer maestros that are able to readily and easily form oxidized and reduced forms of themselves. In its oxidized form (NAD+), NAD accepts electrons from other molecules, which results in it becoming reduced and forming NADH.
If, for instance, you look at the Krebs or citric acid (or tricarboxylic acid cycle (TCA)) – all names for the same thing – you’ll see NAD+ or NADH again and again – because they are major outputs of the cycle. The NADH produced in the TCA cycle then kicks off electron transport chain activity by donating electrons to Complex #1. The upshot is that NAD’s nimble redox activities allow it to play a key role in energy generation.
NAD (in blue) plays a key role in the Krebs or citric acid cycle. (From Wikimedia Commons).
NAD also acts as a coenzyme in redox (reduction/oxidation) reactions and plays a role in the ubiquitous ADP-ribosylation reactions that are involved in many cellular processes (cell signaling, DNA repair, gene regulation, apoptosis.) NAD+’s regulation of two enzyme families (PARPS, sirtuins) also allows it to coordinate the strength of the inflammatory response and fight off pathogens. Some believe NAD+ boosters may function as anti-inflammatories and pathogen fighters.
Plus reduced NAD+ levels may prevent a cell from producing an effective response to a pathogen. Several viruses (HIV-1, herpes simplex virus 1, hepatitis C, and the SARS-CoV-2) have been associated with lower NAD+ concentration in immune or muscles cells. Other studies suggest that the metabolic pathways associated with NAD+ get highly upregulated during coronavirus infections.
Mitochondrial Supplement?
A small Finnish study found that NAD+ supplementation helped people with mitochondrial myopathies. That was intriguing as both mitochondrial myopathies and ME/CFS share the unusual characteristic of exercise intolerance as well as muscle fatigue and weakness. The symptoms in mitochondrial myopathies are often first noticed around the age of 20 when a person develops exercise intolerance or muscle weakness. The National Institutes of Neurological Disorders and Stroke (NINDS) description of “exertional fatigue” sounds uncannily like ME/CFS/FM.
“Exercise intolerance, also called exertional fatigue, refers to unusual feelings of exhaustion brought on by physical exertion. The degree of exercise intolerance varies greatly among individuals. Some people might have trouble only with athletic activities like jogging, while others might experience problems with everyday activities such as walking to the mailbox or lifting a milk carton.”
Symptoms can vary widely and can include some not often found in ME/CFS such as stroke-like episodes, problems with eye mobility, droopy eyelids, hearing loss, and others. Depending on the tissues affected, mitochondrial myopathies can cause a multitude of symptoms.
Different forms of mitochondrial myopathies exist, but in general, they’re described as “neuromuscular diseases caused by damage to the mitochondria”. Because nerve cells in the brain and muscles require the most energy, they’re the most likely to be affected.
Several case reports suggest that mitochondrial myopathies may, at times, be masquerading as FM or ME/CFS. In 1999, an Italian group described a case of mitochondrial myopathy misdiagnosed as fibromyalgia. Dr. Ambrus described a woman with mitochondrial myopathy and fibromyalgia who responded to mitochondrial supplements (which did not include NAD). Similarly, in 2015, a Spanish group described a 30-year-old Ph.D. student with ME/CFS who was found to have mitochondrial myopathy.
The tests needed to ferret out these issues are rarely done in either of these diseases.
The Finnish Study
Niacin turned around several mitochondria and muscle findings in the FInnish Study.
Niacin isn’t often thought of as a mitochondrial supplement, but mouse models suggest that mitochondrial myopathies are associated with reduced cellular NAD+ levels. The recent Finnish study, “Niacin Cures Systemic NAD + Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy“, appears to have been the first study to assess niacin in mitochondrial myopathy – but will surely not be the last. Biopsies revealed 2fold lower levels of NAD+ in the muscles of mitochondrial myopathy patients.
The participants started off with 250 mg/day of niacin a day and ramped up to 750 (for the smallest participant) or 1,000 mg/day for 4 months. They were asked to take the niacin with a light meal in the evening. The healthy controls were monitored for 4 months and the mitochondrial myopathy patients for up to 10 months.
A slow-release form of niacin was used to avoid flushing, but upon reaching 500 mg/day, everyone in the trial experienced flushing. Over time, though, the incidence of flushing declined. A few people reported flatulence, gastrointestinal irritation, and skin drying.
The study found that 750-1,000 mg/day of niacin over 10 months in people with mitochondrial myopathy, and for 4 months for 10 healthy controls, raised blood NAD+ levels dramatically (7-fold for patients and 5-fold for healthy controls).
Over that period of time, the muscle NAD+ levels of the mitochondrial patients reached those of the healthy controls. (That the muscle NAD+ levels did not increase in healthy controls indicated they already had optimal NAD+ levels). Muscle mass, however, was increased in both groups without any weight gain.
Interestingly, niacin also significantly reduced the ‘‘unhealthy’’ fat deposits in the liver and the body by 50% and 25%, respectively, in the patients. Niacin supplementation didn’t decrease total cholesterol levels but did decrease levels of the unhealthy LDL cholesterol in the mitochondrial myopathy patients.
The patients also showed remarkable increases in muscle strength (10-fold in abdominal muscles, 2-fold in back muscles, 2.5-fold in upper extremities (shoulder and elbow flexion strength) but just a slight improvement in the 6-min walking test. While maximum oxygen or exercise capacity did not improve during a cardiopulmonary exercise test (CPET), lactate levels after exercise were reduced. While some patients reported they were able to exercise better, most did not.
Niacin supplementation also increased most of the amino acids in the patients’ muscles, and levels of creatine reached normal levels over time. Gene expression revealed a widespread downregulation of the mammalian target of rapamycin (mTOR) – a mitochondrial inhibitor.
Slight reductions in hemoglobin concentrations, and decreased red blood cells, suggested that niacin “suppressed slightly erythropoiesis or iron metabolism”. Vit B12 decreased and then rebounded over time. The authors underscored the need for “special attention to hemoglobin concentration and blood counts”.
Endothelial Cell and Blood Vessel Support
Given the possibility that damage to the endothelial cells may be contributing to ME/CFS, fibromyalgia, and long COVID, niacin’s ability to vasodilate the blood vessels could be producing the increase in energy and clarity I sometimes experience.
Some evidence suggests it might. A higher dietary intake of niacin was associated with greater endothelial functioning among healthy middle-aged and older adults. A 2014 review found niacin therapy significantly improved endothelial functioning (flow-mediated dilation) and that higher doses of niacin (≥ 2000 mg/day) were the more effective. A 2019 review asserted that niacin and nicotinamide riboside should be considered “critical components of combination therapies to slow the vascular aging process and increase cardiovascular health span.” One study highlighted the improvement seen in the “microcapillary network”.
Longevity
Reductions in mitochondrial NAD+ have been found in neurological diseases and aging.
The discovery that NAD+ levels decline as we age has sparked considerable interest in using NAD precursors like niacin to increase longevity, combat neurodegenerative diseases, etc. NAD+ declines have been associated with numerous neurological diseases, including dementia and Alzheimer’s, and studies are underway to assess the effects of NAD+ boosters.
It appears that an NAD+ decline locks in a “pseudohypoxic state” that disrupts oxidative phosphorylation; e.g. energy production. Interestingly, this pseudohypoxic state occurs even in the midst of normal oxygen levels.
In 2013, a Harvard NMN (nicotinamide mononucleotide) study that was able to return the mitochondria in the muscles of older mice to a younger state really got the ball rolling. The authors reported:
“Our data show that 1 week of treatment with a compound that boosts NAD+ levels is sufficient to restore the mitochondrial homeostasis and key biochemical markers of muscle health in a 22-month-old mouse to levels similar to a 6-month-old mouse.”
Five years later Sinclair linked NAD+ depletion with a reduction in capillary formation and was able, using nicotinamide mononucleotide (NMN), to restore blood vessel growth, muscle functioning and endurance to mice.
Age-related changes in blood vessels could mirror the changes that occur more rapidly in ME/CFS and long COVID. Several findings, after all, suggest that people with ME/CFS or post-COVID-19 are aging more rapidly than expected.
Age-related blood vessel changes result in increased coagulation (a possibility in ME/CFS and long COVID), damage to the microvascular barrier (possibly promoting the leakage, aka Systrom’s work), and the reduced release of vasodilators from the small blood vessels – thus possibly reducing blood flows (Wirth and Scheibenbogen) to the mitochondria in the skeletal muscle, heart, and central nervous system.
One form of niacin quickly reversed age-related declines in muscle functioning in older mice by restoring endothelial functioning, increasing blood vessel elasticity, increasing mitochondrial activity, and ATP production, and reducing inflammation. A 2022 review “NAD+ in COVID-19 and viral infections” proposed that the decline in NAD+ levels seen body-wide during aging may be one reason older people are more susceptible to serious coronavirus infections.
Niacin, it appears, is being studied in many clinical trials including one to determine if it can improve recovery from exercise (reduced lactate levels among others.) At least 9 trials are assessing niacin in COVID-19 patients, including one that’s combining low dose naltrexone with niacin.
Treatment
Diet
Enriched flours are fortified with niacin (Vit. B3). Meat (chicken, liver), fish (tuna, sardines, salmon), poultry, enriched and whole-grain bread, fortified cereals, edamame, avocado, and broccoli have been reported to be particularly high in niacin.
Supplementation
Niacin comes in 4 forms – each of which produce the crucial element – NAD (seen above) – in the body.
Niacin
Niacin or nicotinic acid is actually an oxidized form of nicotine but has vastly different functions (and is not addictive). The word niacin was created out of the words nicotinic acid and vitamin in order to differentiate it from nicotine. The goal in taking niacin is for it to be converted into nicotinamide adenosine dinucleotide or NAD – an essential “energy enzyme” which plays a role in many biological processes.
Niacinamide
Niacinamide is structurally closer to NAD – the compound we want to increase in the body – and is more easily converted to it. Nicotinamide also does not cause flushing, which some find disturbing.
The Gist
- I have intermittently experienced significant periods of mental clarity and energy improvement while using niacin (Vit B3). (Those episodes may (or may not) be associated with the flushing that some forms of niacin produce.)
- Niacin in its various forms produces NAD in the body – a key compound that plays a role in numerous processes including energy production. NAD exists in various forms depending on whether it’s been oxidized or reduced. Its ability to easily pick up and discard electrons has made it a central player in Complex 1 in the mitochondria.
- A small Finnish study found low NAD+ levels in patients with mitochondrial myopathy – a disease that shares several features with ME/CFS/FM including exercise intolerance. Several case studies have described FM and ME/CFS patients with mitochondrial myopathy who benefitted from mitochondrial therapy involving niacin and/or other supplements.
- While exercise intolerance was not improved in some patients, increases in blood and muscle NAD+, muscle strength, muscle mass, and amino acids, and reductions in unhealthy fatty deposits and lactate during exercise were seen.
- Other studies suggest that niacin may be able to help with endothelial functioning; i.e. increase blood flows through the small capillaries that provide nutrients and remove toxins from the tissues.
- “Niacin” comes in four forms: niacin, niacinamide (NMN), nicotinamide ribose (NR), and nicotinamide mononucleotide. The first form, niacin, can produce a hot flushing sensation that usually declines over time. It may be the most helpful blood vessel enhancer. The second form, niacinamide, is more efficiently metabolized into NAD and does not produce flushing. The third form, nicotinamide riboside, may be the most effective mitochondrial enhancer but is more expensive. The fourth form, nicotinamide mononucleotide has been most associated with longevity research.
- Still, other studies indicate that NAD+ declines occur as we age and NAD+ precursors such as niacin may be helpful in reversing some of the aging processes. This is an active area of research.
- NIacin appears to be mostly safe but at higher levels and over longer terms may cause side effects in some and liver tests should be done. (See blog)
- All in all, with its good safety profile, its ability to affect the mitochondria and open the blood vessels, and possibly affect longevity, niacin presents an intriguing possibility for those trying to enhance the activity of their mitochondria.
One alternative health website reported that using nicotinamide or niacinamide instead of niacin does not open blood vessels wider nor provide a cholesterol-lowering effect. It’s believed the flushing effect allows the toxins stored in these fatty tissues to spill into the bloodstream and get processed out of the body.
Nicotinamide mononucleotide
Nicotinamide mononucleotide is the form of niacin most associated with longevity and anti-aging. It’s what Sinclair twice used to turn back the clock in his animal studies and appears to have neuroprotective properties. A 2021 clinical trial found that NMN actually improved muscular insulin sensitivity in prediabetic women. Studies are underway to assess its effectiveness and safety in humans.
Nicotinamide riboside
Nicotinamide riboside (NR) is a synthetic form of nicotinamide that may be able to increase coenzyme NAD+ levels more efficiently than either niacin or nicotinamide. It may also be helpful in preserving the telomeres. It’s also quite a bit more expensive. Dr. Ambrus reported that he uses NR in his metabolic myopathy patients.
Takeaways
If you’re using niacin to vasodilate the blood vessels, use niacin. If you’re using it to enhance mitochondrial production, to support skin health, or for other reasons, try niacinamide or nicotinic riboside.
Dosage
Verywell Health recommends taking 3 grams daily (divided up into small doses) for 12 weeks for osteoarthritis. For acne, take supplements containing 750 mg of niacinamide combined with 25 mg of zinc, 1.5 mg of copper, and 500 mcg of folic acid once or twice daily.
RxList reports that 3 grams per day of niacinamide can result in liver problems or high blood sugar. A naturopath recommended taking 500-3,000 mg/day broken up into at least 3 sessions a day. (Niacin has a short half-life in the body.)
The National Institutes of Health, on the other hand, asserts that taking 1,000 mg/day can lead to low blood pressure, tiredness, high blood sugar levels, nausea, heartburn, and abdominal pain, and blurred vision:
- Extreme tiredness
- High blood sugar levels
- Nausea, heartburn, and abdominal pain
- Blurred or impaired vision and fluid buildup in the eyes.
Several websites recommend getting periodic liver function tests (serum aminotransferase levels) when taking high doses of niacin (1,500 mg/day or more).
Sauna Therapy
Niacin is often used in combination with sauna to support detox. One sauna detox site recommends slowly (50-100 mg implements at first) working your way up to 2,500 – 5,000 (!) mg of niacin per detox session so as to keep the flush going.
Decades ago, I did a 6-week sauna detox program at Dr. Rea’s Environmental Health Center in Dallas. I don’t remember if they used niacin, but everything else was similar. Supplements to support detox were given, and a 25-30 minute bout on an exercise cycle – which I tried but had to give up – got the toxins flowing, which the sauna session was designed to flush out. Even doing the minimum amount – 1 sauna session a day – was grueling. (This was before infrared saunas). Six weeks of that left me in considerable pain, but a couple of days later while driving back to the West Coast, I felt an unusual sense of clarity and well-being.
Risks
Although niacin is often described as being completely safe, there are some warnings associated with long-term use, particularly at higher levels. Long-term use of niacin led to increased insulin resistance in a rodent given a high-fat diet. (In contrast, in 2017, a delayed-release form of niacin improved markers of insulin resistance and metabolic inflammation.)
The Mayo Clinic warns people with liver disease, peptic ulcer, or severe low blood pressure about taking large amounts of niacin (2-6,000 mg daily). People with allergies, gallbladder disease, symptoms of certain thyroid disorders, diabetes, and gout (niacin can increase uric acid) could also find their symptoms exacerbated.
A naturopath recommended that the dose be lowered if nausea occurs and that people taking large doses of niacinamide (>/= 1,500 mg/day) should have periodic liver function tests (serum aminotransferase levels) done.
Conclusion
NIacin is not a godsend but it presents an intriguing possibility for those going the mitochondrial supplementation route. It’s considered safe at moderate doses, helped people with mitochondrial myopathy in a small trial, is engaged in a wide variety of important processes, may be able to help with blood vessel flows, and has been linked with longevity. It’s also quite cheap (in its niacin/niacinamide form).
Those using the non-flushing form may not receive the blood vessel and detoxification effects while those going with other forms might receive better mitochondrial effects. Nicotinamide mononucleotide is most associated with anti-aging and studies are underway to assess its effectiveness and safety.
The Mitochondrial Enhancers for Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Series
- Pt. I: D-Ribose, CoQ10 and PQQ
- Pt. II: L-carnitine and Acetylcarnitine
- Pt. III: Magnesium
- Pt. IV: N-acetyl cysteine (NAC)
- Pt V: Oxaloacetate
- Pt. VI: Niacin, Nicotinamide, and Nicotinamide riboside
- Coming up Metformin, Rapamycin and ?
Wonderful summary as per usual!
Your experiences seem also consistent to me with picture that mito underperformance is downstream of actual hypoxia, e.g. due to micro clots or autonomic vascular dysfunction (the Systrom theory). Mito supplementation would then seem compensatory rather than addressing root cause.
Btw, I’ve had the strong immediate but only sometimes response to several things, including Nattokinase and oral rehydration. It’s a real puzzle!
Right now I’m going with the hypoxia/blood vessel scenario but that pseudohypoxia in which NAD+ reductions cause oxygen uptake to be diminished even in the face of abundant oxygen levels sure is intriguing. I wonder if Naviaux folds that into his Dauer hypothesis.
I definitely need to experiment more with niacin – get more organized in how I test it (any organization at all would be a step forward, actually) and assess different kinds.
I have a similar experience with oral dehydration – most of the time it helps but not all the time.
Dr. Lonsdale’s book goes into detail on the pseudohypoxia mechanism. His ideas seem to fit well in here.
A word of caution based on my personal experience. I had no fatigue symptoms or CFS and came down suddenly with CFS-POIS simultaneously after taking 4 grams of SLO-NIACIN for 3 months given to me by PCP in 1993. The 3 grams were already making me feel very stressed and almost depressed. And in my ignorance after eating a fatty pizza, to “make up” for it i took half a pill more. A total of 6 grams!! The next day I came down with CFS. I was given this treatment because my cholesterol was 250. I stopped Slo-Niacin. The symptoms the day after the high dose were chest pain on left side, bloating, severe gastrointestinal distress, paleness, and extreme weakness. Instant food intolerance and sensitivities. I think it is very likely the Slo Niacin caused my blood irrigation to become so limited then that I could hardly walk. I also wonder if the high dose triggered an immune (auto?) response due to the high levels of Slo Niacin (to get rid of it). Or perhaps it was the wrong kind of Niacin that triggered an imbalance. I also read that Niacin can affect the mechanism by which the body recognizes itself. 30 some years of CFS later I regret the day I was given this treatment and my taking Slo Niacin for something as trivial as moderate cholesterol. What a price to pay. Be careful. There is more to the Niacin topic that meets the eye. It is very complex. I still think that if I figure out how this high dose triggered CFS in me I may find a way to address it.
Dilation in my opinion is at the center of CFS and POIS.
I have had mild ME for nearly 9 years, it was severe at the start but over the years I moved to mild. Caught covid in December and came down with long covid end of January, symptoms have ranged from vascular problems heart issues, insomnia neurological issues, severe gut issues loss of libido amongst other symptoms. I have started a protocol that includes high dose niacin and r alpha lipoc acid, b vitamins and methionine, this is making a huge difference. The r alpha lipoc acid is important in the protocol. In the space of 3 days at a dose of 500mg flush niacin and 500mg r-ala I have seen improved sleep, less pain, improved neurological symptoms, improved mood, return of libido and improvement in gut function. There are alot of people in the telegram group I am in reporting similar experiences. The flush is bothersome at the start but when i added in the r-ala I don’t flush at all.
Thanks for sharing that Colm – and good luck!
Thanks Cort and keep in the good work your site has been a beacon of hope to me over the last 9 years.🙏👍
I have found NMN and NAD+ are both helpful. NR doesn’t work at all, and niacin and niacinamide aren’t very direct.
Hi Colm,
Thanks for sharing your positive experience with niacin. In what way did it help with sleep? Did it help with brain fog/daytime drowsiness?
I have gone from sleeping one to two hours a night to sleeping 6 to 7 hours and my sleep feels more refreshing. After you take you dose you can feel your head clear.
The guy who came up with the protocol is an epidemiologist who was looking into dementia and alzheimers and looking into receptor gpr109a which niacin binds to. His theory involves leaky gut, lack of butyrate producing bacteria low melatonin and low Nad you catch covid or some other virus and this leads to further depletion. I have swallowed nearly every known probiotic to man and nothing has helped my gut as much as this protocol in 4 days and it has not probiotics in it
He has shared alot of scientific papers (way beyond my level of understanding) with us showing niacin affect not just on Nad but t cells and the immune system, and inflammtion.R-ALA is key as it helps the niacin get into the cells, otherwise you have a lot of niacin in the blood causing not very nice flushes.
Hi Colm, Are you working with Dimtry or just doing things on your own? This was April, how are you doing today and did you stay with this protocol? I am currently taking 500mg 3x day. But nothing else with it. Thanks!
Round and round goes the merry go round always looking for some form of treatment for a multitude of symptoms instead of looking at what causes CFS and now long Covid. As a lot of people have already said in comments it is reactivation of Epstein Bar Virus which which the immune system response is to attack causing chronic inflammation hence all the symptoms. The only way to test for active viral infection EBV is a PCR DNA test as EBV serology test is not reliable. Funny how all cancer research is only looking for treatments and not for cause and cure.
It would be nice if it was so simple. If Ian Lipkin hasn’t been able to find it my guess is that it’s not there – at least in its normal form. I’m leaning to the smoldering herpesvirus idea. EBV is there – just in a strange form and its not fully replicating so they’re missing it.
https://www.healthrising.org/blog/2018/11/17/could-crippled-herpesviruses-be-contributing-to-chronic-fatigue-syndrome-me-cfs-and-other-diseases/
Loebel e.a. 2014
Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893202/
Unfortunately, yours is an outdated and scientifically unproven opinion. Wish it were so simple. In my company’s research, no EBV was detected. Lerner and Stanford U. have looked at EBV and never could demonstrate a connection or a satisfactory treatment regimen. While I know nothing about Niacin, and my research has pushed me in a different direction,(FM, IBS, Long COVID) the jury remains out with all conditions of the somatic symptom disorders orders, especially ME/CFS.
Which lab does Pcr EBV testing? Any recommendations. My PCP only runs blood serum ; Labcorp.
Thank you
I wonder in you can mix up/alternate the different types of Niacin? to get the same effect ? use a tolerable amount of the regular Flush Niacin to get the flushing and blood flow effects, some nicinamide to get the mito effects and seems “niagin” is the brand name for Nicotinamide riboside (expensive version). ?
Yes decades ago at Dr. Rea’s center niacin was used in combination with the exercise bike and sauna for detoxing. I did not get there, i had intended to go but broke my leg
How’s your NAD+ level, Cort? I wonder if there is any study done on NAD+ level in CFS patients.
The NIH website defines “exercise intolerance” for mitochondrial myopathies as “During physical activity, muscles may become easily fatigued or weak”. That is rather different from the exercise intolerance of CFS with the bill coming due the next day in the form of post-exertional sickness that lasts days or weeks. Not being able to exert because muscular fatigue or weakness is more like exercise inability.
So many ‘gears’ working all at once, with everyone having different amounts of different products and byproducts.
Chem labs were so easy because SOME ITEM was always the ‘rate limiting’ step.
Microbulomics may need to give patients individual testing, before and after eating a specific amount of very specific food(s), to start to quantify results better.
As well as using Dr. Alain Morneau’s unique massage stressor to quantify the exercise done, too.
Cort . It is that simple I have ME/CFS and have pathology reports for EBV serology IgM positive on numerous occasions and I also had a PCR DNA test for active viral infection with results showing EBV DETECTED.
It’s encouraging that you can have a noticeable reaction to the niacin Cort. I do take 50mg Vit B3 as part of a multivit but that isn’t at a very high dose. I do remember though, when I was really struggling to get any energy, that foods that seemed to ‘get through’ were beef liver, chicken, turkey and peanuts. I have some sort of issue with peanuts now, so I can’t eat them, which is a pain because they were great at one time.
I do think that some of my issues are blood flow related, so the nutrients and oxygen, are just not getting where they’re needed. I was struck by your sentence “Because nerve cells in the brain and muscles require the most energy, they’re the most likely to be affected.”
Years ago, my legs were likely to collapse under me, if I tried to walk too far. Thankfully that’s not the case now but my brain doesn’t have the same level of stamina I had before. I used to have seemingly unlimited brain energy and could have all sorts of thoughts going on at the same time, on different levels (probably too many!)
Though I’ve improved a lot and can access all areas, for short periods (as long as I haven’t set my immune system off) I run out of energy too soon. So, reading longer pieces, is more difficult, especially if I’m tired. I can only get so far into the article, before I’ve run out of energy. But I’m fairly busy and can keep going, at a steady rate with rests, for most of the day now, which is great. I’d just like more reliable access to my brain’s processing ability back.
Interesting comment about the feeling of your legs collapsing under you. I have had that for the whole time I have had this illness (luckily a mild form of it). But interestingly walking has never really been a big problem, it’s more sustained running or trying to play a sport with sustained running where that’s a problem. My legs just give out.
I don’t try and run anymore. I can walk though, whuch is great, but I don’t push it. Like I used to have loads of energy and could walk up hills, swim etc. But now I don’t have the energy to walk up hills. Maybe if I wasn’t doing all the other stuff I do, I may be able to. I’ve found if I do too much then I feel like I’m a sinking ship. Best avoided. It’s my brain that runs out of energy quicker, if I try and process too much information. I’m okay with relaxed chit chat though.
Hi Cort, Thanks again for a great article.I think I’m going to try this for my hands which are very weak from ME neuropathy. I’m not sure which form to start with though. Maybe the flushing one and ala like Colm said? You mentioned that muscles get stronger but the exertion threshold doesn’t seem to improve. Did I get that right? I could use more muscle strength. But does anything change the exertion threshold for the better? I lost ground this year. I’m not bed-bound, but getting closer
I agree with the comment that ME/CFS and long Covid appear to speed up aging. That’s certainly what it feels like. After 2 years of it I feel 10 years older.
Great article ! I have pretty severe exertional fatigue. The two things that have helped me the most are NADH and d- ribose. While NADH supports complex I in the ECT I recently started PQQ to support complex 4. I’m trying to whip my mitochondria into action !!!!!
As always, this is great, Cort. I’d like to have the diagram poster-sized to be able to really study!
I find this whole area of NAD, NR, NAD+, glutathione, very confusing. My CFS doc (yes, I’m lucky) gives me glutathione shots weekly. My lung doctor is happy about that, but says that I don’t have to take NAD+ because I’m already getting glutathione shots. My CFS doc says I have to take the NAD+ too, because “it does something different.”
I had a severe bilateral ear pain reaction to a continuing HVAC noise outside and the neuro-ear doc told me to take — in addition to the glut shot and the NAD+ – L Acetyl Cysteine almost like a prednisone-pack: 2,000 mg bid for 2 weeks, then 1,000 mg for 2 weeks, down to 500 daily “if I want.”
Confused about what to do, I wondered about taking NMN and started the experiment today: 300 mg sublingually on empty stomach, away from thyroid supp.
Going back to a blog you did in 2021, one of the commenters said her COPD sx were alleviated by taking NAC. When I was on my super dose regimen, I think mine were too.
But it is very confusing to try to figure out how to navigate all this. I’m hearing that taking NAD+ isn’t absorbed as well as NMN because, the argument goes, NAD+ has to convert into NMN and it can be hard for the body to do that.
Perhaps you address all this in your blog above, but I didn’t see my particular questions addressed.
Should I go back up and reread it a few times?
Thanks.
Correction: neuro-ear doc told me to take N-Acetyl Cysteine – put the L in the wrong place.
How is r-ALA different from ALA? I started taking 300 mg daily of ALA because my B6 levels were way too high. Within 3 months, the ALA brought the B6 levels down, but I don’t notice any symptom improvement.
ALA increased my liver enzymes . I had extremely high B6 levels too and I went on a low B6 diet drinking coconut water and 3 litres of H20 a day with salt
It’s a good question: studies do not find muscle weakness in ME/CFS but those studies as I remember measure fatiguability over a short period of time. Two day exercise studies do indicate that exertion in ME/CFS impairs the ability to produce energy; i.e. it produces some weakness but it appears to be different.
Other symptoms of mitochondrial myopathy like drooping eyelids have not been reported in ME/CFS in my experience. Mitochondrial myopathies, however, can cause so many different symptoms that I question whether the absence of some means much. I question whether all forms of mitochondrial myopathy have been uncovered as well.
Have you seen this RCT published in Cell a few years ago?
https://linkinghub.elsevier.com/retrieve/pii/S1550-4131(20)30190-X
Please see my other message below… it takes more than just flush niacin, in the sense that we have to restore and harness the ability for niacin to do what it needs to do…
Thank you so much for bringing more awareness to the main causative treatment component to yes finally cure these hells, including ME/CFS, CF, and long COVID. The key though—along with flush niacin—will be the combined administration of mainly R-lipoic acid (make sure to get the right kind), all the other B vitamins, beef liver, l-serine for a boost, and for so many (even if they eat meat), meeting the growing demand for l-methionine (as an immune boost and to re-establish the whole methionine flux down through cysteine to glutathione to taurine). I have been curing pretty much everyone now from these conditions/diseases and quite rapidly. I understand many are uber-sensitive to flush niacin at first, but these aforementioned components will make it smooth from the get-go, quickly allowing one to build up to the needed dosing. It comes down to needing to re-modulate back up the niacin GPR109A receptor, which after for many, not just long COVID but decades of unaddressed inflammation led their cells now to carry so much oxidative stress & gunk that the cellular functioning is unable to restore its current into signaling to the niacin receptor how much gunk there is for niacin to clear, most of the niacin administered (until the aforementioned other treatment components, mainly R-lipoic acid) will not be going into the cells/hitting its receptor properly, explaining the bothersome sensitivity reactions still.
I can dive into all this in much more detail, so for the sake of brevity in here, please join our community on Telegram (HOM3OSTASIS) for the full protocol and conceptual framework (for free of course) and/or follow me on Twitter (dmitry_kats). I am more than happy to help end each and everyone of your suffering. It is readily possible and probably now. This isn’t a joke or a scam, by any means.
Thank you,
Dmitry Kats, PhD, MPH
Reply to Gijs , everyone should read the link supplied at the bottom of Gijs comment including you Cort .It pretty well spells it out what has gone wrong. Not only with M/E CFS but other diseases lupus and multiple sclerosis and probably a lot of the autoimmune diseases which the medical profession always says we don’t know what causes them.
Dimitry if it is free, please could you put your protocol on here for us. I tried to get in to your link but it said address not recognised. Or if it is too long perhaps you could write it in a separate blog. If it is helping so many people please share, we all need help. Thank you.
H O M 3 🦋 S T A S I S
https://t.me/HOM3OSTASIS
That is the telegram group link. I believe he will have a website up and running soon.
Thank you Colm, that is the link I tried but it said address invalid!
That’s weird… I can add you manually – DM me on Twitter (dmitry_kats) – like tag me, and then I’ll reply
One of my doctors recommended NADH some years ago, based on the positive experience of another patient. I take 20 mg sublingual and it had an immediate and noticeable improvement on my physical functioning. If I overdo (rare, as I’m really careful, but it happens), I take a second tab and it seems to more quickly alleviate the lactic acid aftereffects that otherwise linger with PEM.
Not got a twitter account Dmitry
Niacin + Creatine
twitter.com/NiacinCreatine
Hi there,
There is a lot of talk about niacin as a way to help manage LDL cholesterol, as you touched on.
However, there is some talk about niacin taken whilst on statins can increase the risk of statin myopathy / myalgia.
On the other hand there are some studies that talk about using them together as a therapy – and in fact my MedSafe datasheet for Simvastatin specifically mentions using niacin with it.
I wonder if this is worth mentioning in your article –
We gotta realize that LYME/MOLD hog up NAD+ so. Most CFS patients are sick from MOLD and LYME.
Hello,
If CFS May be caused by EBV virus: how can this be treated effectively?
Frank
Anyone tried Tru Niagen? It is an NR
supplement – at acceptable cost.
And it does not cause flushing. However, it seems my CFS symptoms only get worse (especially disturbed sleep) and now I’m planning to quit after 17 days.
Dr. Klimas is using it in her latest GWS study. Encouraged about its mitochondrial healing potential, I got a bottle. It is pricey; after two weeks did not see much difference, but it might take a few months to realize results. Instead, I switched to Energy Needs for a balanced mito boost, a 40-ingredient supplement designed by an autism MD for those with autism and other neuro issues, including Parkinson’s and other conditions. Three weeks in and clarity, motivation, and energy seem to be enhanced. Will give it two months. Sure keeps the supplement clutter at a minimum, though. Check out the website.
Beca – I looked for Energy Needs and can’t find it. What website were you referring to?
Ericka: Neudoneeds.com is the company
Ericka: Neuroneeds.com
Melatonin is also being used & there is a Brain condition that plays a big role in Melatonin, insomnia, fatigue, brain fog, memory concentration vertigo the symptoms are long it is called a Pineal Gland Cyst or Tumor.
I went back to looking at my MRI’s & I found a Pineal Gland issue, the normal values are 0.5 to 0.8cm & my Cyst or Tumor now is 2.4cm/24mm x 1.8cm/18mm
I am now waiting to see what my Doctor suggest & a lot of Doctors call these incidental but they are not they do cause issues & disabilities.
There are few Surgeons globally who do this Surgery one in the USA is Dr. Patel I think he is at UNC in North Carolina.
They open the skull back of head or on top & do Robotic type Surgery to remove the Cyst or Tumor they are rare to be cancerous but are tested for this during Surgery.
Mine now is about 15/16th of one inch I will post more here once I know more, MRI Contrast is best by MRI without can see these.
I am not sure if CT Contrast can be used but ask. I have seen these in Families they may be Genetic & one can be Birn with these…
typo above ‘Born with these’…
After reading this, I thought “why not?”, and ordered myself some niacin. I’ve been taking it now for a couple of weeks, and I’ve had more energy than I’ve had for longer than I can remember. It’s a very busy time for me, as I’m standing in the local elections in the UK, so I’ve been out canvassing at least 4 times a week (door knocking, talking to people) something that normally would wipe me out completely! I’m carrying on taking the niacin!
I have been trying NIACIN for years but never exceeded 500mgs a day. Once I got up to 1.5grams a day and added Betaine HCL I started to see benefits right away.
I would say my energy and mood has improved by 20%
I have ordered TMG and I intend to add that methyl donor
If niacin does not work, perhaps add Betaine HCL or TMG?
I appreciate this post (but…) I don’t understand this takeaway “If you’re using niacin to vasodilate the blood vessels, use niacin. If you’re using it to enhance mitochondrial production, to support skin health, or for other reasons, try niacinamide or nicotinic riboside.”
The Finnish study used Nicotinic Acid to repair mitochondria. NA is the only Niacin to bind with GPR109A. Why point people to the forms of Niacin that are unrelated to the very successful study?
(I’m starting to think those other forms of Niacin were only created so they could be patented.
BTW: How are you doing?
Ha! I just started taking a small dose of niacin for its vasodilating properties. (I have an autoimmune condition that causes my cerebral arteries to constrict abnormally.)
I chose it because I am already taking the max I can tolerate of vasodilators that work by other means, but I still need a bit more blood flow.
And then of course I find out that other folks have been doing that for ages!