Studies suggest mitochondrial problems are present in ME/CFS and FM. Could supplements help?
Health Rising’s fourth IACFS/ME conference overview is also its fifth in a series on possible mitochondrial enhancers in chronic fatigue syndrome (ME/CFS) and fibromyalgia.
Like the last overview on n-acetyl-cysteine (NAC), this supplement – called oxaloacetate (OAA) – does not appear in Lee Know’s book “Mitochondria and the Future of Medicine”. The supplement is unusual in other ways: for one, it’s rare that for an “omics” study to spark an interest in a new treatment or that an experienced ME/CFS doctor has gotten excited about a supplement.
Health Rising’s 2021 IACFS/ME Conference Overviews
- “A Huge Problem and Major Crisis”: Avindra Nath on Long COVID at the IACFS/ME 2021 Conference
- “Emerging Options for Autoimmune ME/CFS”: Scheibenbogen at the 2021 IACFS/ME Conference
- “IACFS/ME Conference 2021 Pt. III – the Exercise Studies: Long COVID Moves Closer to ME/CFS, Metabolomic Weirdness, Two Symptoms to Rule Them All”
Oxaloacetate (OAA)
Dr. David Kaufman, MD, clearly watches the ME/CFS research literature closely, and when he saw that Arnaud Germain’s 32-person 2017 metabolomics study found a significant depletion of oxaloacetate, and was the main metabolite found to affect energy issues in ME/CFS, he acted. Kaufman got in touch with a manufacturer and set up his own in-house study.
(Check out Germain’s presentation of a recently completed, larger ME/CFS metabolomic study at the IACFS/ME conference.
When oxaloacetate (OAA) is reduced to malate, it generates NAD+, which plays a role in many cellular processes. It plays a role in gluconeogenesis, amino acid and fatty acid synthesis, and the Krebs/citric acid cycle that produces most of our energy. It’s reportedly able to cross the blood-brain barrier and is sometimes used as a nootropic. Animal trials suggest it may be activating mitochondrial biogenesis pathways and enhancing antioxidant and brain insulin signaling pathways in the brain.
Kaufman’s OAA ME/CFS trial did not have a control group, but Kaufman proposed that the placebo effect in his patients is probably quite low as they’ve generally tried many treatments with little benefit.
After emphasizing that his results were preliminary, and noting that no control groups were used, Kaufman called oxaloacetate’s effects “extraordinary” and highlighted its support of mitochondrial biosynthesis, reduction of inflammation, and enhancement of NAD and NAD+ in the Krebs cycle.
Kaufman tracked the results in 52 patients. The average age was 49, 77% were women, and the average duration of disease was 6.1 years. Patients who’d had the disease as long as 30 years participated in the study.
Unusual Results
Half took 500 mg 2x’s a day and a half took 1,000 mg 2x’s a day. Three surveys (Chalder Fatigue Scale/Fatigue Severity Score/PROMIS Fatigue) were done at 2 weeks and 6 weeks. Kaufman said many are continuing to do their surveys 6 months later.
At 500 mg/ 2x’s a day, the Chalder Fatigue Scale score dropped significantly within 2 weeks and then dropped a bit further. By 6 weeks, it had dropped about 25% on average. The Fatigue Severity and Promis fatigue scores dropped less – by from about 5 to about 15%.
At 1,000 mg/ 2x’s a day, the Fatigue Severity Score didn’t budge much, while the PROMIS Fatigue Score dropped by about 15%. Again, the Chalder Fatigue Scale score dropped further by about 35% (to the low 60’s). Kaufman reported that his patients wanted to stay on the drug and many have been reporting their scores to him 6 months later.
The Fatigue Scales
It’s not clear why the scores should differ so much, but Dr. Kaufman believes that the Chalder Fatigue Scale, the only one developed for ME/CFS, is probably the most accurate. If you’re interested, check them out below.
Chalder Fatigue Scale
The Chalder Fatigue Scale was developed for ME/CFS and has been around since the early 1990s. Three versions exist. One version asks the participants to rate their answers to the below questions on a 0-3 scale.
- Do you have problems with tiredness?
- Do you need to rest more?
- Do you feel sleepy or drowsy?
- Do you have problems starting things?
- Do you lack energy?
- Do you have less strength in your muscles?
- Do you feel weak?
- Do you have difficulties concentrating?
- Do you make slips of the tongue when speaking?
- Do you find it more difficult to find the right word?
- How is your memory?
Fatigue Severity Scale (FSS)
The FSS was developed in 1998 to measure fatigue in neurological diseases like multiple sclerosis. The participants use a 7-point scale to report whether they agree or disagree with the following statements:
- My motivation is lower when I am fatigued.
- Exercise brings on my fatigue.
- I am easily fatigued.
- Fatigue interferes with my physical functioning.
- Fatigue causes frequent problems for me.
- My fatigue prevents sustained physical functioning.
- Fatigue interferes with carrying out certain duties and responsibilities.
- Fatigue is among my three most disabling symptoms.
- Fatigue interferes with my work, family, or social life.
The PROMIS Short Form Fatigue Profile
The PROMIS fatigue score was developed for rheumatoid arthritis and has gone through various iterations, including one created specifically for fibromyalgia. The PROMIS fatigue score was developed for rheumatoid arthritis and has gone through various iterations, including one created specifically for fibromyalgia. I don’t know which one was used. It asks participants to answer questions such as “I feel fatigued”, “I feel tired”, “I have trouble starting/finishing things because I am tired”, “I have energy”, I am able to do my usual activities”. “I need help doing my usual activities”.
“Striking and Surprising” Results
Dr. David Kaufman (on the left) questioning a presenter at the 2018 Dysautonomia Conference
Kaufman – who’s been in this business for quite a while now, and has tried every treatment under the sun – called the results “striking and surprising” and durable as well. More also appears to be better with this supplement: the response appears to increase with the dose.
Calling the numbers “very significant”, Kaufman reported that 80% of patients reported an improvement – not something he usually sees in any intervention for ME/CFS. Some people showed very dramatic reductions in fatigue – by as much as 80%. Increases in well-being are being reported as well, and side effects are rare (a rarity in ME/CFS).
Dose appears to matter. Although the study did not track them, at 1,000 mg 3x’s day, Kaufman stated fatigue improved even more and referred to a 55-year-old man who’d had ME/CFS for 10 years and who received few gains at 500 mg/2x’s a day but whose fatigue plummeted (from 60-20 on the Chalder scale) when he took 1,000 mg/3x’s day.
Kaufman hopes to get funding to do a placebo-controlled trial. He’s also working with a company to do the metabolomics needed to assess oxaloacetate levels before and after supplementation.
When someone asked if supplementation to boost NAD as well would help, Kaufman replied that boosting NAD would be a good thing but is a difficult thing to do.
The worm in the ointment is the cost. You can purchase oxaloacetate online, but it’s very expensive – probably around $5-600 a month at the higher, more effective doses. The oxaloacetate Kaufman (Jubilance) used can be found here. (It’s advertised as a PMS/mood supplement.)
Kaufman, who seems to attend every conference possible, and appears determined to unearth every treatment option possible, also reported on New Frontiers for ME/CFS at the IACFS/ME conference. Kaufman was the doctor who enabled Jeff to break the craniocervical instability (CCI) issue in ME/CFS. Now he’s leading again with the oxaloacetate supplement.
The supplement’s high cost will undoubtedly put it out of reach for many, but one wonders if a successful placebo-controlled trial could change that. Time will hopefully tell how well oxaloacetate works in ME/CFS. If OAA is, as Kaufman believes, uniquely effective in ME/CFS, that in itself should help us learn which parts of the mitochondria (or other systems) are primarily affected in ME/CFS.
ME/CFS and Long-COVID Oxaloacetate Studies Under Way
OAA studies are being pursued in Alzheimer’s, ALS, myasthenia gravis, cancer, ME/CFS and long COVID. The long-COVID double-armed, randomized, double-blinded placebo-controlled trial is being funded by the same company (Terra Biological) that provided the supplement to Kaufman. It will consist of 40 patients taking 500 mg 2x’s/day. Contact: Alan B Cash (858-947-5722), acash@TerraBiological.com.
Check out two ME/CFS OAA trials in this blog.
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, Niacinamide and Nicotinic Riboside
I have to say that the Fatigue Severity Scale seems to be much more pertinent to my experience of ME/CFS, capturing the impact of exertion and the decrease in function. The Chalder Scale looks like it mainly captures “drowsiness” or lethargy, something I don’t associate with ME/CFS at all. “Wired and tired” is a much more common experience than drowsiness, for me. Gosh, sometimes I wish I could feel drowsy. Unfortunately, for me, this makes me skeptical about the usefulness of this supplement.
Agreed. Post-exertional malaise should be the priority symptom to tap.
In order to assess PEM, though, you need a validated instrument. Each of these scales have been validated through studies. I don’t know if there is one for PEM (???)
I continue to be amazed by the information you present to us Cort.
Thank you for all you do.
I have tried jubilance (100mg oxaloacetate). It is sooo helpful. The tight, strangling feeling in my legs is gone for short walks. Plan on keeping with it.
Hi do you mind me asking if you’re still taking this supplement, please and are you buying it from the main manufacturer where it’s very expensive?
I was surprised that there was so much difference between the scales which is why I checked them out. Dr. Kaufman’s experience is that the Chalder scale most accurately represents what he’s seeing.
I have been dealing with ME, for almost 30 years. I have also been diagnosed with Polymialgia and Seronegative Rheumatoid Arthritis. Why is Severe Chronic Pain, not being discussed? The fatigue is a constant, but I suffer from a Sleep Disorder. “Wired and tired”, is a perfect description. Sometimes I can’t sleep for 3 days. The pain is crippling, but was manageable with Pain Medication, muscle relaxants, antidepressants and a benzodiazepine for over 25 years. I have gone through two bouts of Viral Meningitis, which IS caused by “Fibromyalgia”. Before I found a team of Neurologists, who recognized my symptoms immediately, I had been hospitalized three times for suicide attempts. I was told, that the obscene pain and brain fog was caused by a mental disorder! I went through hell and back, before finally seeking out Dent Neurology.
These men saved my life. Now, with NYS has completely destroyed Chronic Pain Management. Physicians are terrified to prescribe medications, which make it possible for any quality of life.
I am now facing a very bleak future, due to the misuse of opioids for recreation. The problem was never prescription Oxycontin, which does not produce a euphoric effect, and contains fillers to prevent crushing or chewing. With the recent conviction of the most highly respected Neurologist/Pain Management Physician, Patients who have followed every rule, are in desperatation. Medical Marijuana is not the answer for many patients. Individuals who are in desperate need of help,
are being cut off of pain medication completely, or tapered to a ridiculously inadequate dosage. Now comes the problem of Qualified Pain Management Physicians, leaving their practices. Psychiatrists are not qualified to deal with neurological or immunological disorders. In my personal experience, my pain medication was lowered to a barbaricly low dose. Treatment with Medical Marijuana was attempted twice. At an our of picket cost of 1000.00 per month, and the other medications still needed, that avenue was not viable. After reading extensively about possible treatments, my Neurologist/Pain Specialist readily agreed to try a 5mg, therapeutic dose of prednisone.
This worked wonderfully for the Polymyalia. With his sudden departure, I was shuffled off to a Nurse Practitioner for a Psychiatrist. I was immediated cut of of Paraphin Forte(an extremely effective muscle relaxant for ME), and prednisone. My primary care physician immediately prescribed the prednisone and a less effective muscle relaxant. My ability to atrend any family event, or even do my own grocery shopping has been taken away. Very recently, I was informed that my pain medication will be cut off, if My Physciatist continued my benzodiazepine. In the past, my specialists communicated with one another, and agreed upon my treatment. I was attempting a slow wean off if prednisone, due to the adverse effect if weight gain. I am now, simply “Collateral Damage”. Suddenly my diagnosis of Seronegative Rheumatoid Arthritis is being called into question. This diagnosis was confirmed by two primary care Physicians, and two Neurologists, who observed the flares over twenty years.
I am running out of time. Being scolded by Nurse Practitioners, who insist that I will stop breathing, if medications I’ve taken correctly, for over twenty years is absolutely infuriating.
I am not alone. While others are turning to buting street drugs, others are choosing suicide. The issue needs to be addressed NOW!
The same thing is happening to me. I’m at my wits end. What will it take suckers, illegal drug use ?? I can’t function and no one will listen. Now what??? Scared in pain and losing it!
This all happened to me as well, I couldn’t function so I plaid their game and went on suboxone. I will say it has helped me the most with my pain and I was up to 500mg morphine equivalents!! They also let me stay on my benzo. I go through Ideal options they have clinics everywhere and can do visits over the phone. They have a Facebook page as well so u can call them with questions anytime.
What the government and doctors have done to us is so traumatic and uncalled for. Please I was on fentanyl patches. Ambien. Benzos all at the same time and never had issues. The real thing is heroine made a comeback!! So stupid
Kind of sounds like you have this rare genetic metabolic bone disorder called Hypophosphatasia. You can tell easily by looking back at your blood work/labs – if you have chronically low ALP it’s almost always a hallmark for this disorder. Most doctors have not heard of this disorder – you would need to get to an endocrinologist.
You are absolutely right. I am blessed to have a good pain doctor who prescribes methadone and hydrocodone. I worry all the time that he might stop. I would die, too. They are forcing chronic pain victims to commit suicide or go to street drugs…it is evil. I hope you find a better pain doctor.
I found this researching oxaloacetate for my constant fatigue, but at the correct doses it is too expensive. I have found pain relief in PEA or palmitoylethanolomide…must be micronized. Is affordable. Can increase dose until you no longer feel increased pain relief then back off to previous dose. Take with a healthy fat, like raw coconut oil and Alpha Lipoic Acid R fraction….start at three a day, can increase every week or wait a month. I felt decreased nerve pain in two weeks. Give it three months, but I would at least double dose if nothing after a month. Vitality has a thirty day guarantee, but when I emailed them since it says give it 90 days he said he would increase guarantee to 90 days for me. Please, try it. Lots of studies for a supplement.
Hey Agatha, I realize that your comment is from a few years ago, but I just started the jubilance oxaloacetate two weeks ago and one of the first things that I can say it definitely helped with was removing the “wired” from the “tired” if that makes sense lol it took me about a week to be able to put my finger on it but it’s like I recognize when I’m tired and I actually take a break instead of just doing one more thing and one more thing and then the spiral continues. I also have been able to notice what I’m doing my PT and I’m compensating in a different area and stop myself instead of trying to correct it and convince myself I can push through it which tells me I’m thinking more Clearly, pretty incredible results for the first week. I’m two weeks in now and I can tell that my energy is definitely better during the day even though I have been getting less sleep, which pretty normal for me on any supplement like this. I hope you see this and it helps you 🙂 and I hope you’re doing well. Take care.
Thank you, Sara! I appreciate you sharing your experience. I continue to rely on pacing and supplements, feeling wary of medications until there are more studies to show long-term effectiveness. I wish you very well on your journey, and I’m glad to hear that oxaloacetate is helping you. I’d be interested to hear over time how things progress! Thanks again.
What dose are you taking?
Hi Cort. Could you please clarify the typo on costs- hundreds or thousands per month? Thanks
Dr. Kaufman said $5-600 per month. That’s about what this source (https://www.ebay.com/itm/264018331113?mkevt=1&mkcid=1&mkrid=711-53200-19255-0&campid=CAMPAIGNID&toolid=10029&customid=CUSTOMID&msclkid=8db5335d26ce11ec8b3b017aa4aff38d) on Ebay would cost if I figured it out right.
Thank you Cort
Actually, unless I’m missing something, to take 1,000mg/day would mean taking an $50 entire bottle every day.
Did you mean to say, in the article, that the top dose was 100mg/day?
250 mgs/tablet x4 = 1000 mgs x 3 = 12 tablets a day. Is that right? Here’s a link to the oxaloacetate Kaufman used – https://jubilance.com/. One good thing – you would probably know within 2 weeks if it’s working. It might get better as you went on but you would know within a couple of weeks. That was my impression.
I am seeing it’s only 100 mg of oxaloacetate per pill (and the rest 150 mg of vitamin c).
Great catch! Have to be careful though. Kaufman used Jubilance which has 100 mg OAA and 150 mg Vit C. Does the 1000 mgs 3 x’s a day mean 1000 mgs of OAA or 1000 mgs of the pills OAA comes in. Since Kaufman said it would cost $5-600 a month. I assume he’s referring to the total mgs of the pill.
Money aside, oxaloacetate dose aside, 12 Jubilance tablets per day is 1800mg of Vitamin C per day. 2000mg of Vitamin C is the maximum safe daily dose.
https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/vitamin-c/faq-20058030
Perhaps this is no coincidence. That is, this is the maximum safe daily dose of an existing supplement that can be divided by three. Accordingly, this represents 3 x 400mg of oxaloacetate a day.
By contrast, 3 x 1000mg of oxaloacetate a day delivered by Jubilance would mean 4500mg of Vitamin C a day. So I believe that possibility can be ruled out.
BenaGene also appears to have exactly the same constituent make up as Jubilance (by mass that is). Both mention thermal stabilisation of the oxaloacetate. Both reference exactly the same patents:
USA 9,561,199 & USA 9,050,306.
So it looks to me like they are different badges on the same product. BenaGene is saying that it ships outside of USA/Canada for a minimum order quantity of 2 bottles. Jubilance only mentions shipping within USA/Canada. However, I’m guessing that with a potential benefit to Long Covid sufferers, this might be about to go gangbusters, if it hasn’t already.
USD$40 (with subscription) for 30 tablet bottle on the parent company website.
https://aor.us/products/benagene/
However, they are sold out. Hmm, ominous.
The products are also available through specific product branded websites and Amazon from what I can see.
So for a 30 day month, you would require 12 bottles. Which would be USD$480.
It was stated that taking 1,000 mg THREE times per day produced even better results.
I am currently participating in Dr. Kaufman’s trial, so I can give a bit more information here.
On the front of the bottle of oxaloacetate, it states, “90 capsules 500 mg”, implying that each capsule contains 500 mg of oxaloacetate. However, on the back of the bottle, it says the following:
Serving Size: 2 capsules per day.
Amount Per Serving
Oxaloacetate 500 mg
No Vitamin C is mentioned.
Nevertheless, the information on the front and back of the bottle seems to be contradictory. Does one capsule contain 250 mg or 500 mg of oxaloacetate? Both Dr. Kaufman and the manufacturer refer to the doses in a way that implies that the capsules contain 500 mg of oxaloacetate. I am taking 2 capsules 3x/day, as the lower dose didn’t do anything noticeable for me. Both Dr. Kaufman and the manufacturer have referred to my current dose as 1000 mg 3x/day.
At this dose, I can say that oxaloacetate has been extremely helpful for me, and it is definitely one of the most effective drugs I take. It has made a real positive difference in my health, and I hope it is made available to everyone at a reasonable cost.
Hi Steven, I just wondered how you are doing with the supplement now? Thanks very much!
hello Steven, I just started oxaloacetate today (500 bid) and I feel like my heart is in my throat. will this go away as my body acclimated?
I never experienced this symptom, so I can’t really say.
Thank you so much for responding! I feel quite jittery and almost like my POTS isn’t well controlled after only 1000 mg today. Guess I’ll try 500 mg daily for a week and then try to increase and see how it goes! Thanks again!
Hi Steven. How are you doing now with the oxaloacetate? Has your level in energy stayed the same if you stopped taking it? I would greatly appreciate an update.
Thanks Steven for bringing some if not final clarity to this situation and continued good luck with the supplement.
Hi Deborah, I to have been suffering for 27 years. I have the same exact complaints with the medical field. They think it is all in your head. That is a complete insult to me. I have cried many days and nights. Your whole story is my story to the exact. I suffer sleep issue to the exact. It seems to me there is a lack of communication between the medical professionals. Iam not sure where you are at but I am in a state with medical insurance is overwhelmed. I can see the difference in the last 30 yrs for sure and I look for it to get worse, unfortunately. I can’t believe your story mirrors my own. I agree change must happen now. The question is how? I wish you all the best .Take care.
I would gamble on trying the higher dose for $500, but I can’t find it for less than $1,000.
Does anyone have a more affordable source?
This one looks cheaper but I am not sure if it is food grade. The description seems to suggest it will be used in tests. I also don’t know which countries it ships to.
https://www.sigmaaldrich.com/GB/en/product/sigma/o4126?gclid=CjwKCAjwkvWKBhB4EiwA-GHjFvrnd1t1eCE2IFhE2Y1Y7VwM4cFCTiPmaIReAuqQ_uD3rabSA_AMaBoC8TkQAvD_BwE
Thanks Diane — it looks like this company has offices worldwide.
Diane,
May I ask how you found this company? I thought I was good at searching—obviously not good enough 😉
I place an order but I’m not confident that they’ll approve it. Based on the info that they wanted it seems that they are a supplier for businesses.
Ah, looking closer it seems that this product is not “thermally stabilized.”
I found it using this search term: bulk “oxaloacetate”
It is the only alternative source that I can find that might sell to individuals. The only other source that I could find only sells to laboratories.
It seems that “Terra Biological LLC nor any other company have disclosed their methods for stabilizing oxaloacetate” [1]. So I doubt that you will be able to find stabilised oxaloacetate anywhere.
It would also seem [2,3] that oral oxaloacetate at 200mg doesn’t get into the blood. So interested individuals would be best buying smaller quantities from Sigma Aldrich and injecting it. It is not clear to me if subcutaneous injections are adequate or if intravenous would be required. It seems that there really isn’t much human research to go on as far as oxaloacetate is concerned.
[1] https://supplements.selfdecode.com/blog/oxaloacetate/
[2] https://pubmed.ncbi.nlm.nih.gov/4884771/
[3] https://onlinelibrary.wiley.com/doi/pdf/10.1111/jnc.13509
On the Jubilance website, there is a banner at the top of the page asking if you are looking for oxaloacetate for me-cfs, to click on a link that takes you to this page:
https://benagene.com/product/oxaloacetate-cfs-90-count-bottle
It has bottles of 90 capsules at 1000 mg for $499. There is no Vit. C in these capsules.
Kelly, the patent application that Cash filed notes how they “stabilize” OAA. Mixing with with a hygroscopic compound–calcium carbonate, the same substance used in cheap antacid. Then it is combined with a sweetener and a compatible pill compound and a preservative.
Alan cash in you tube video saying that it is available as a food grade product for cfs /me patients but your doctor would have to oversee your use
go to
Medicaid supplements
in your state
From Jubilance website I was led to this site:
https://benagene.com/product/oxaloacetate-cfs-90-count-bottle
It has bottles of 90 capsules at 1000 mg for $499. There is no Vit. C in these capsules.
You can purchase the larger dose oxaloacetate supplement Kaufman used in his trial (formulated specifically for CFS as a “medical food”) here:
https://benagene.com/product/oxaloacetate-cfs-90-count-bottle
Bulletproof KetoPrime has 100mg of oxaloacetate along with C and B12.
Bulletproof’s supplement is $50 for 30 x 100mg pills on Amazon. At that rate, it would cost $1500 to take 1000mg 3x daily.
BenaGene has the high dose OAA for ME/CFS patients for $499 and requires a physician to prescribe.
Wouldn’t NADH work equally well?
Thanks for this interesting article, Cort. Kaufman’s patients are lucky to have him as their doctor.
I priced things out based on the cost of the source, Jubilance, that Kaufman used in his study. The source on eBay seems to be about as expensive when shipping costs are included.
At the lower dose of 500 mg twice daily, you would need to take 10 capsules daily (each capsule contains 100 mg of OAA) or 300 capsules (10 bottles) monthly. That would cost either $420 or $490 depending on whether you buy at Jubilance’s “subscription” price of $42 per bottle or the retail price of $49 per bottle. To do a 2-week trial at the lower dose, you would need to buy 5 bottles at a cost of $245.
The cost of the higher dose, which means taking 20 capsules a day, would be $840-$880 each month. To do a 2-week trial at this dose, you would need 9 bottles at a cost of $441.
Let’s hope this pans out as beneficial to ME/CFS patients in a double blind study and that the cost of this supplement comes down.
Yes, on the surface it sounds somewhat promising but we need proper trials. Perhaps if it was shown to be effective, and therefore produced at greater scale, the cost may come down ( he says hopefully…)
Thanks Mark for sussing that out. Hopefully we will get a good trial and then we’ll see if that makes any difference with price or insurance company reimbursement. (Do they ever cover supplements?). Glad to see a long COVID trial already underway.
Cort,
(i initially misunderstood, but then realized ‘plummeting fatigue’ means amount of fatigue decreased alot)
is there anyway to know how long the oxaloacetate stays in the body, or how fast it is absorbed into the bloodstream?
while it seems dose dependant, i wonder if there is a possibility that the higher dose somehow stayed in the bloodstream longer, so that trialing a sustained time release may mean the dose can be decreased.
i dont know if there is a form of oxaloacetate that is safe to be given iv, but it might give some answers on how fast it disappears from the bloodstream, and what an effective dose is.
and if it gives the same sort of results– two weeks– perhaps some bright light can do mechanistic computer simulation to see what it might be changing or doing for those two weeks before results are seen.
(or metabolomics to see)
(where it might be seen that, for example, until blood pH hits a certain point, or some other point is reached, before the good effect starts)
great to hear potential good news…….. for the more good potentials, hopefully some will pan out and be successful
this site i believe is in Canadian dollars,
https://aor.ca/product/benagene/
and says:
“NPN80039432
Discussion: benaGene® contains the first (and patented) thermally stabilized oxaloacetate, a key intermediate in the Krebs Cycle which is involved in cellular energy production. benaGene® provides superior antioxidant protection for the maintenance of good health.”
then for ingredients:
“Supplement Facts
Serving Size: One capsule benaGene™ (3-carboxy-3-oxopropanoic acid) 100 mg Vitamin C 100 mg
Non-medicinal Ingredients: microcrystalline cellulose, sodium stearyl fumarate.
Capsule: hypromellose.”
(info above i just copy/pasted)
apparently some foods have a little
present too:
not sure if its the same form?
from site:
https://healthjade.net/oxaloacetate/
“Oxaloacetate food sources
Oxalacetic acid can be found in a number of food items such as daikon radish, sacred lotus, cucurbita (gourd) and tarragon, which makes oxalacetic acid a potential biomarker for the consumption of these food products.”
Here is the US site:
https://benagene.com/product/oxaloacetate-cfs-90-count-bottle
1000 mg, no Vit. C.
The product they are testing is 250mg per capsule with no additional ingredients.
How do you know that? Can you paste a link to the study?
Again, an interesting compound! When we talk about “mitochondrial” or “metabolic” effects we often think: our cells now produced more energy and this is why fatigue subsides etc. But as we know, ME/CFS may be more complex, in its root ME/CFS is a neuroimmune disorder, i.e. it is about immune dysfunction/inflammation control and their consequences on regulatory CNS functions. So how could oxaloacetete fit into this picture? Here some indication from basic research:
Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis: https://academic.oup.com/hmg/article/23/24/6528/608261
As a summary of their research: oxaloacetate may in fact reduce neuroinflammation.
It wouldn’t surprise me if there’s something happening with patient gut flora here, particularly concerning the glyoxylate cycle (https://en.wikipedia.org/wiki/Glyoxylate_cycle). Two enzymes, isocitrate lyase (ICL) and malate synthase, found in bacteria & fungi but not in animals are needed. Notably, candida albicans is virulent due to the ICL activity (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004578/). ICL converts isocitrate to glyoxylate, which is converted to troublesome oxalate in the cytosol of human cells. Normally, glyoxylate is formed in the mitochondria and mostly further converted in there. (Side note: coenzyme-A is involved in multiple steps, so might be significant)
So if glyoxylate can be absorbed in the gut and make it all the way to circulation & into cells, it can become oxalate, which is associated with many pathologies. I’m not really sure how oral oxaloacetate would impact the glyoxylate cycle here though, so this is just something to keep in mind or look into.
I learned about this after getting results back from the GPL Organic Acids Test done twice, years apart. Both times they showed high oxalate levels, over twice the high mark. I definitely get the symptom of a sudden stabbing pain in my eyes (thankfully not too often). GPL’s site has several pages about oxalates (here’s a brochure: https://www.greatplainslaboratory.com/s/GPL_Test_OAT_Oxalate-Control-3pge.pdf).
I don’t know if this is related, but I immediately feel a little better by drinking vinegar, which is absolutely disgusting but anything that works even a little is great. It’s acetic acid & its conjugate base is acetate. Acetate + oxalate would be oxaloacetate, but I haven’t found anything that says that reaction takes place. The plant enzyme oxaloacetase does the reverse (although that’s reversible like most reactions).
All in all I really don’t know if this info will pan out, but the gut flora products need to be accounted for in order to fully understand our biology. I’d update the old adage thusly:
– You are what you eat… plus what your gut flora produces from that
The coupon site Honey has a promo code for the Jubilance site. If you sign up for the recurring shipments-which can be cancelled anytime-you can get the first bottle for 19.95 instead of 42.00 by using promo code try-for-19.95. The code doesn’t work if you try to order just a single bottle-has to be the recurring shipments. I tend to be very sensitive to meds and supplements and this is at least a cheaper way to see if I can tolerate this supplement. Thanks Cort for all your information!
Thank you so much, Deborah. I just ordered the way you suggested. I’m really sensitive to things, so I will probably start very low and see how I respond “sesitivity-wise” (e.g. 1 pill or even 1/2 at very first). I’m also doing low dose Abilify, so not sure if there will be any interactions/enhancements with that. (Improved memory would be a great thing, tbh. )
Thank you, Cort for all this information. And, also thanks to other members providing links/info/cost breakdowns.
I’m wondering if anyone else who will try this is also doing Low Dose Abilify???
Thanks and good luck!
Sudden stabbing pain in the eye. Me CFS sufferer of thirty years. On a scale 1 to 7, I’m a 7. Mostly housebound. Can you tell me in layman’s terms, I can’t absorb complicated info.! just what this means. Thank you so much.
Anyone interested in going halves on a kilo? https://www.ingredientmall.com/antiagings-c-4/oxalacetic-acid-oaa-oxalacetate-highest-purity-at-wholesale-price-1kgbag-p-2312.html
@John,
Given the high price I had a similar idea and found this site, a direct manufacturer in Shanghai;
https://herbnutritionals.com
I’m thinking perhaps it might be a good idea to wait for more information about the efficacy of this supplement rather than the results from such a small study. Meanwhile I’m tempted to just order a bottle from Jubilance and see how I feel after a couple of weeks. After some bad experiences with ‘continuing shipments/cancel at any time’, I’m not so sure about a cheap trial bottle. If it does prove to be a game changer, then maybe we all can organize some sort of ‘buyers club.’
On another topic, I had my Covid booster yesterday; sore arm, tired, and interestingly enough, the teeth which have had work done (gum surgery and root canals) are achy. I remember reading that some who had cosmetic fillers put in, experience similar.
Thank you again Cort!
I would be interested in teaming up with you people for discounted pricing. I probably want to wait for more info to come in.
This sounds promising!
If we get 5 people then that is 200g each for say $400 by the time it is shipped/divided and shipped again. based on 3g – high dose used in study – it would be a 2 months supply per person or at the low dose a 200 day supply. I saw would be game if we can get 5-10 people
We can consider it citizen science
It’s not heat stabilized, thus it won’t be absorbed well enough to work.
I would probably go for it, but Im from Czech Republic
A clarification from Terra Biological—Oxaloacetate is still under study, and has not received approval from any Regulatory Agency for the treatment of Chronic Fatigue Syndrome. Currently, the dosage used in the initial research is higher than suggested in the nutritional supplements “benaGene” and “Jubilance” (100 mg oxaloacetate capsules in a 30 count bottle).
For the ME/CFS patient, who will work with their doctor, more information can be obtained at http://me-cfs.info. Your doctor can work with you to coordinate care and over-see dosing levels using 500 mg capsules of oxaloacetate.
A “Medical Food” is different than a nutritional supplement– the term is defined in section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b)(3)). A prescription is not required to purchase a medical food, but it’s use must be overseen by a doctor, who will help set dosages.
More information at
http://ME-CFS.info
Hi Alan,
Somehow missed reading this post until after posting about your 500mg Benagene product (and quoting the email you sent me last Friday). 🤦♂️
Impressed that your in the trenches so to speak for your clientele.
Best wishes! 🙂
Thanks for that clarification! So it is 1000 mg of the active ingredient oxaloacetate and they are using specially formulated capsules that are not available on Amazon.
Is anyone using the product from http://ME-CFS.info successfully?
My husband likes to point out that I have a drawer full of supplements that I heard about; tried and just couldn’t tolerate.
Now I always check reviews on Amazon and while some may be fake, on balance, they give you a reasonable overview of the product.
Oxaloacetate is marketed under brand names other than Jubilance. The Jubilance brand actually has four reviews all for positive for PMS.
Amazon’s Choice is Benagene and has 131 reviews that may be useful to Health Rising readers. I would definitely look at the 3 star and under reviews.
If I’m understanding correctly –
his patients take a considerable dose of the marketed product
which has vitamin C in it as well
So how can you separate what is doing what:
maybe the vitamin C is doing something too…
Has this been accounted for in his studies?
Vitamin C – depending on the form – used to be one of my lifesavers. It got rid of that feeling that a truck drove me over when I woke up, the fatigue and the joint pains.
Woke me up like no amount of coffee did, etc.
It really depends on the C supplement though – this one was liquid.
I don’t need it anymore.
I guess this is as good as any a place to mention
Madora’s adventures with intramuscular C
https://lessflexible.com/treatment-that-works
and
Way before her, decades ago, patient zero for ascorbic acid:
Norman Cousins with IV C, drip drip drip drop an hour
a continuous flow of it.
His case sounds a lot like ME/CFS, and his profile (sensitivity to medicines, connective tissue stuff, etc, etc)
It’s a short read:
https://archive.org/details/AnatomyOfAnIllness
Note the mode of administration.
Also, ascorbic acid in his time (and the formulation Madora uses) may have been a very different product than the ones formulated in OTC supplements. Different source /manufacturing processes.
I think there are better ways to go on about correcting redox states etc,
and less invasive
and easier to access
The supplement that is being used in Dr. Kaufman’s study does not have vitamin c in it. My friend just received her supply which is
Oxaloacetate 500mg
(Thermally Stabilized Oxaloacetic Acid)
Veggie Capsule
How does one get into that study? When I do a search on clinicaltrials.gov I do not find it.
Dr. Kauffman said during the Q & A that he uses Terra Biological which makes Benagene. He was unclear on whether the dosage referred to the active ingredient of oxaloacetate or the entire capsule.
I decided to assume it was for the capsule since that’s clearly marked on the front of the bottle and took 1000mg of capsules (400mg oxaloacetate) twice a day for two weeks. He said patients would feel effects in two weeks. That cost around $200 from Amazon.
I felt no different, better or worse. Disappointed, but not surprised. I’ve tried other mitochondrial supplements to no avail. My dysautonomia medications so far provide the largest and most obvious benefit.
So I’m not sure if I should try again with a pure oxaloacetate or not.
Attek, what are your dysautonomia medications that are providing you with the large and obvious benefit? Thank you!
I take fludrocortisone and desmopressin for orthostatic hypotension & low ADH (anti-diuretic hormone). I had frequent urination which was very dehydrating.
When I’m on them, I can function at about a 70% level, doing light activity for about 10 hours a day. I did a trial off them for a month to make sure they were necessary and helpful. My health declined and I was on the couch most of the day with the flulike exhaustion, about a 30% level. Within a week of restarting them, I had regained my functioning level.
What medication are you taking for dysautonomia, please ?
Me too, I get no benefit from mitochondrial supplements.
Thank you !!!
Benagene also has an “Oxaloacetate CFS” product where the capsules are 500mg of just OAA – NO vitamin C at all. The cost is $499 for 90 capsules.
https://benagene.com/product/oxaloacetate-cfs-90-count-bottle
I purchased a bottle and will be starting them this morning.
I also contacted the company about promotional codes or discounts. The CEO / Founder of Benagene (Alan Cash) wrote back:
“At this time, we do not have a promotional discount for this product. However, if you order this through your physician, they may pass-on the wholesale price to you. Your physician/health professional can contact us directly for pricing.”
Thanks for passing that on Bakken. Good luck!
Cort can u tell me of any reported side effects from oxaloacetate s?
Thanks! I’ll ask my doctor about it.
Do you know if the discount would be for all countries or just US?
Brent, have you noticed any difference in your health since taking this supplement?
Hi do you have an update?
Hey Jess,
I didn’t receive any noticeable change to my symptoms during the use of that limited supply. Since there wasn’t any perceived improvement, I refused to shill out additional hundreds for further testing and “treatment”.
That being said, I’m personally in the mostly mild range of symptoms and can work 30 hours per week. This product may work for others where it was ineffective for me.
Hope that helps.
The more that I look into this, the more concerned I become about the snake oil involved.
First, there are abundant examples of deficiencies that cannot be correct by direct supplementation. This deficiency is what prompted Kaufman to try OAA but OAA is not a good candidate for this. It is negatively charged at both ends which prevents it from entering cells. To get molecules like this into cells you have to convert them into methyl or ethyl esters.
Secondly, even if you could get the OAA across cell membranes and into cells the proposed mechanism of action makes no sense at all. The ultimate source of NAD+ is NADH. The concentration of NAD+ is 700 times greater than NADH so if you converted ALL of the NADH in a cell to NAD+ you would only increase the concentration by 0.14%. I can’t imagine that a one part in 700 increase would be significant but even if you could do that you would kill the cell because NADH is actually required for other vital processes.
Finally, the experiment is bullshit. The justification for not using controls is just nonsense. The easy counterargument being that did the patients try all their other treatments within the format of a trial??? Not using controls, especially in this situation, is lazy at best – fraudulent at worse. The only reason not to is to game the results and to make them look as good as possible to non-scientists. The amount of work and effort involved in adding controls is particularly insignificant in this situation when you realise just how expensive the supplement actually is!!! The expense of the supplement would also make the use of controls that much more important because if positive results were obtained then telling people about them would drive many many people to buy the supplements. This whole thing is highly unethical for that reason alone.
I really have to question Kaufman’s ethics here. It seems to me that either he is devoid of them entirely or his head is so far up his own ass that they just are not on his radar. Dirty trials like this just don’t deserve the light of day.
When it comes to poor science PWME can’t have it both ways. We can’t moan about the poor science in PACE and then jump on every little shitty experiment that offers us hope simply because it offers a positive result. Shit is still shit no matter how it is packaged.
I should also add that it would seem that oral oxaloacetate at 200mg doesn’t get into the blood. [1,2] IF (and that is a big IF) oral OAA is beneficial then it seems unlikely to be working in the way suggested. So Stephen R Collier above would be on the right track with his idea that this might actually all be about the gut flora/microbiome.
[1] https://pubmed.ncbi.nlm.nih.gov/4884771/
[2] https://onlinelibrary.wiley.com/doi/pdf/10.1111/jnc.13509
I understand the desire to have everything buttoned up but the reality is that this is a small field that get little funding. We have to start where we are.
Try and put yourself in Kaufman’s shoes. He’s a very busy ME/CFS doctor with a huge workload, yet after he found this substance, he got the company to provide it for his patients and worked up the results. How many ME/CFS experts have gone to such trouble over the past 30 or 40 years? I can count the number of instances where a doctor has done something like this on the fingers of one hand.
If we were to discount every possibility because it’s not validated by large, rigorous trials we would have a really small medical toolkit to work with.
In his talk Kaufman noted the lack of healthy controls and called for a larger placebo-controlled study to be done. To that end, he’s contacted metabolomics researchers to attempt to determine OAA levels before and after supplementation before the trial and is trying to get funding.
I don’t know the mechanism of action of OAA but there are several any of which could conceivably be helping.
I would be wary of concluding much from small trials like this but they play a crucial role in moving ME/CFS forward because they pave the way for the bigger, more rigorous trials. Published case reports do the same thing – they provide data that can be used to argue for a bigger trial. You basically can’t get to the one without the other. I would take this for what it is- a possibility – and hope a bigger trial comes out of it.
In fact, it probably already has. I would bet that the Kaufman ME/CFS trial convinced the supplement manufacturer to create the long COVID trial that’s underway.
Cort, you are providing a great service through your site. But let’s assume for a moment that perhaps Mr. Cash “found” Dr. Kaufman in trying to develop niches to make a LOT of money off his supplement, then supplies free supplement to the investigator to appear to make the supplement appear legit. Mr. Cash’s companies have been at this for awhile to profit off of several diseases. But few of the “studies” his companies funded have been independent, which is important. I think there is one recruiting at the Bateman Horne Center at the moment, which has better design. But, for a study to have biases minimized, the researchers cannot be remunerated by the vendor, and should be completely independent and blinded to the arm of the treatment a particular patient is getting until the study is over. That can be done with a supplement just as with a pharmaceutical, and without significant expense. But, the answer may not be what the vendor was hoping for. A couple more legit studies of OAA in other diseases have already failed.
A bigger question is the ethical aspect of marking an inexpensive dietary supplement way, way up and foisting it on a community that is already usually in financial pain. I noted one of your posters already had to restructure his finances to afford the supplement, and this with no guarantee of efficacy. And, I don’t see any financial assistance programs on Benegene’s site like you’d find with a pharma company. This is a play for huge profit based on questionable science, pure and simple. And, no regulation.
Hey Cort…Great written article!…Looks like things are heading in the right direction!…I understand some people’s concerns about dosage and effects, but I think the research is going down the right rabbit hole with looking into the mitochondria/DNA area where the Krebs energy/messaging decoding is happening…Sure, other things have shown in your articles connected to ME/CFS, but this looks promising for going to the heart of the illness…If T3 and other hormones are having trouble absorbing into the cell to get to the ATP to trigger it to work correctly, maybe this direction of research might be a game-changer?…
I found this information exciting – UNTIL I read the following:
https://psblab.org/?p=618
where I learned a great deal of the biochemistry problems and details involved, and also that Dr Cash has a great conflict of interest in his proposed study. So a great disappointment.
Here’s some sentences from the article:
1. As is often the case with the murky waters of poorly-regulated dietary supplements are a number of shortcomings with the actual underlying scientific evidence for OAA’s effects.
2. The claimed mechanism-of-action for OAA is that it drives the MDH enzyme reaction backwards, and this enhances levels of NAD+,
3. First, by using this redox reaction as a source of NAD+, the ultimate source is of course NADH. In cells, NAD+ is normally present at about 700-fold greater levels than NADH. As such, NADH cannot possibly serve as an adequate “reservoir”
4. OAA is a dicarboxylic acid. As such, it is negatively charged at physiologic pH. Negatively charged species are generally excluded from cells.
5. Essentially, non-esterified OAA at a low external concentration will not get into cells, and unfortunately that’s where the MDH enzyme (required for the claimed mechanism-of-action) is located. It’s notable that the only evidence Alan Cash shows for an effect of OAA on NAD+/NADH levels comes from isolated mitochondrial studies in the 1960s, where of course the cell membrane is not present.
Thanks for checking further Jean. Not a happy story there. I don’t have any idea about the biochemistry. The most important thing about the supplement – whatever any thinks about it- is whether it helps or not. For me, I’ll stand on Dr. Kaufman’s experience until something otherwise is proven. A study that is underway in long COVID should help tell us what is what about that disease and hopefully we’ll have one in ME/CFS that gives us some really solid data.
Here is a key to understanding why medicines and supplements tend to work differently, sometimes even producing the opposite effect, in ME/CFS/FMS/hEDS/weird diseases:
“Negatively charged species are generally excluded from cells.”
Our cells’ biology is altered. The electrical charges of the cells, the way they organize themselves, what with the Ca++ stuck inside, the redox balance skewed, etc
And it may be a constant state in some (i.e. the severily ill), it may have rhythms – it may be more pronounced after exertion, it may respond to seasonal changes, diurnal changes, etc.
It may be in certain types of cells/tissues or systemically, etc.
There are many variables that could be involved.
This is what the word paradox really means. It’s not working as they know it to because the underlying physiology has changed (and they are unaware of this).
A sick body organizes itself differently.
You hit the nail on the head there M.
I know there’s a lot of snake oil to beware of out there, but I don’t get why anyone would look at this under the presumption that an ME/CFS body is doing what healthy bodies are expected to do, there’s cell dysfunction at play.
And oftentimes with these supplement studies there’s no way around a conflict of interest because nobody else was gonna sponsor it anytime soon if they didn’t.
And when things DO help notice how the FDA wants them banned, like NAC. Folks put such a horrifically high premium on regulation, when government subsidizes big pharma and actively thwarts our efforts towards good health. Do we really need the glorified mafia to give their stamp of approval or can we decide for ourselves rather than wait around for gov’s permission to feel better?
Did I not just read a recent post about all the damage those government-approved shots did to many of the people on this forum the past few years? If everyone was cool with sticking their arm out for that mess in a tube that leveled the economy and made pharmaceutical companies richer than ever before, no one should be afraid to dig into their own pockets and guinea pig it up for Big Suppla when they’re certainly trying harder to help us than the government regulatory agencies and their deep-pocket pharmaceutical cronies.
Would sending an email to reputed brands like NOW Foods and Doctor’s Best requesting them to manufacture this supplement help? If we mention that CFS patients might need to take it everyday, and that it may even be helpful to Long Covid patients, they might atleast give a thought?
This sounds like a great idea actually. I’d be happy to email too.
I restructured my finances so I could pay at least $500 a month for it, and it’s making a big difference! No relapses! I am pushing where I couldn’t before, and hoping to get stronger. That’s my big question, will it help mitochondria repair themselves enough for my muscles to get stronger. I guess I’ll find out by the end of the winter. I am taking both the benagene and mitachrome versions because the benagene seems more potent but costs twice as much. “Seems” is the key word because I haven’t tried to quantify it, so really don’t know. But I take 1000mg a day of the combination, split in three doses. I’m starting to let myself get excited. I am housebound with ME, bedbound during relapses. I would love to be able to get out of the house and use my electric wheelchair again. Right now my muscles are too weak to sit upright very long. I’m glad to hear that my doctor might be able to order it wholesale from Benagene, and that the benagene version was the one that was used in the study. That’s very helpful.
Whoa! Good to hear Chris and thanks for the update. Good luck 🙂
Hi Chris, tnx for sharing. Could you elaborate a) what exact dosing did you use of your combination i.e. how much of each b) how long until you got noticeable effect c) what aspects/symptoms were most improved d) where do you buy the mitachrome version ?
Tnx in advance, Massimo
Regarding sources of OAA: Apologies if this is redundant—there are too many comments for me to plow through them all! I participated in Dr. K’s trial, but my source of the supplement was not Jubilance. Dr. K set up the trial in collaboration with the owner of the company that manufactures it as beneGene™, Alan Cash. He shipped bottles of supplement for free and an additional supply (if desired) after the study was done. beneGene™ sells it online, in bottles of 90 500 mg capsules. The price is steep, though: $499/bottle!
My personal experience is difficult to interpret. My energy levels did increase during the study period (I took 500 mg twice daily), but the timing was poor as I started the trial just two months after undergoing a craniocervical fusion. So my energy increase could have been the expected result of recovery from major surgery as well as a benefit of the operation.
I’ve continued to take the OAA since the study using the free supply from beneGene™. I hadn’t read about the results until today (thank you for this, Cort!) and was unaware that a higher dose may be more effective. I will consider a trial of increasing to 1,000 mg twice daily.
BeneGene™ sells its “medical food” version of OAA, which is what I was given for the study, online here: https://benagene.com/product/oxaloacetate-cfs-90-count-bottle
The price for the “medical food” formula (500 mg capsules, 90 per bottle) is $499.
BeneGene™ is also selling a version of OAA in the same formula as Jubilance (100 mg OAA &150 mg ascorbic acid per capsule, 30 caps per bottle). It’s available here: https://benagene.com/benagene-shop
The price for this formula currently is $49 per bottle. You can get a discount if you buy 12 bottles of 30: $499 ($42 each).
The “medical food” version (90 500 mg capsules) works out to be less expensive as you would need 15 bottles of the 100 mg/cap version to equal the amount of OAA in the 500 mg/cap bottle, which at the bulk price of $42/bottle would cost $630.
However, if you want to try OAA for just two weeks to see if you get any benefit, at the lower dose of 500 mg twice a day you would need 5 bottles, costing $245. There’s also a lozenge version which has less vitamin C than the capsules (80 mg/tab vs 150 mg/cap). Caveat: please check my arithmetic for yourself!
At these prices, I’d have to experience a life altering increase in energy! Hopefully, if this supplement has a real beneficial effect, increased interest in the product will eventually bring the price down.
This is not an ad. If you live in Canada you can order oxaloacetate via a product by AOR called Benagene, through the Vitamin Shop. It’s expensive but works out cheaper than the Jubilance product. Both products only have 100mg or 150mg oxaloacetate because the other part is vitamin C. I have no connection with either, just sharing info because it took me a while to figure this out. This is an expensive supplement at the doses mentioned in the article but looks like it’s worth a try…
Geoff, the AOR company advertises their product called Benegene as having
100 mg (3-carboxy-3- oxopropanoic acid) and I suspect this is not the same as the oxaloacetate in Jubilance supplement for pms?
Oxaloacetate is a 4-carbon molecule, but can be named systematically in multiple ways. According to ChEBI, oxaloacetate has the IUPAC name of 2-oxobutanedioate. This is the name based on the 4-carbon backbone. But you could also think of OAA as a 3-carbon backbone with two substituents on the number 3 carbon, then it would be 3-carboxy-3-oxopropanoic acid, just as described in Jill’s post.
To me, the more important question is whether all these commercial products are composed of OAA (ChEBI:16452) or enol-OAA. The clinical trial for long COVID is on ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04592354) and explicitly says the treatment proposed is enol-OAA whose ChEBI ID is 17479. This is a tautomer of OAA, which means that the two molecules consist of the same atoms arranged differently. Often, we think of tautomers as being rapidly interconverted, but there is an Enzyme Commission number assigned to the tautomerization of OAA (5.3.2.2.) and proteins from some organisms have been identified as enzymes that catalyze this reaction, strongly implying that cells do not find it trivial to interconvert OAA and enol-OAA.
This is my understanding of a complex topic that goes beyond nomenclature. I’m sorry for all the chemistry in this post, but you have to pay attention to the details, especially when experimenting on yourself.
I cannot resist getting back into this conversation to post my experience with oxaloacetate. And the comments here are all over the calendar, all over the experience realm. I did find some as recent as a few weeks ago, so here goes. Cort, as others say, I appreciate your work on all of these ME/CFS issues, and certainly for this OAA treatment. I originally heard several years ago from my neurologist about it, and was immediately concerned about the price and the lack of choice. However, I tried it for a few weeks, was unimpressed and stopped. At that time I did not catch the 100mg ONLY per cap, and neuro wanted me to increase. I never did follow up with your convo here, and never knew of the medical food version with 500 mg/cap. But I did use the other, and got up to 500mg per dose twice daily. Tried this for 2 weeks but did not notice any improvement. I could not afford to continue. And if the studies actually showed improvement with 1000mg twice daily, perhaps I just did not get high enough of a dose. But even then, with 500mg/cap, thats 4 caps daily, and the bottle lasts barely 3 weeks! I did not see any comments about a medical prescription allowing it to be covered by insurance, and for me, by Medicare. Any feedback here? I will check with neuro, but apparently he was not aware of this larger dose availability. For me, as a retired physician, I have trouble understanding some of the biochemistry, and frankly, it fries my brain to think on it too much! Same goes for the worries about ‘snake-oil’ salesmen. It seems to me that despite the limited studies, at least that was supportive enough for the larger study that Cort cites. Cort, I don’t believe that I have seen any info on that- could you kindly supply a link for that? So although I am disappointed in my own trial, I am still interested (blind faith?) and look forward to their results. I don’t know about you all, but I’m taking about 16 meds and supps, close to 60 pills daily. Ahhhhhhhhhh! It gets pretty discouraging a times. (Sorry for the dump)-)
I understand it helps fatigue and feeling generally better. But did anyone notice their pain improve after taking the supplement? Thanks.
My parent and I have been taking this supplement every day since it appeared on the market, and we’re pleased with the results we see. We have all been feeling o much better and less bloated. This was caused by all of our previous inflammation in the body, that oxaloacetate reduces significantly. We never felt any fatigue ever since we went on the supplement, and we think that’s so great. I bought the oxaloacetate supplement from the same place I buy my prenatal ones, https://www.thorne.com/products/dp/basic-prenatal. I highly recommend it to everyone.
I’m taking this and so far it seems helpful, I will keep posted. My concern is this article titled ‘Oxaloacetate Shenanigans’ https://psblab.org/?p=618 where Dr Brookes states that ‘non-esterified OAA at a low external concentration will not get into cells, and unfortunately that’s where the MDH enzyme (required for the claimed mechanism-of-action) is located. It’s notable that the only evidence Alan Cash shows for an effect of OAA on NAD+/NADH levels comes from isolated mitochondrial studies in the 1960s, where of course the cell membrane is not present’.
thank you everyone for sharing your resources. I am still confused.. Looking at the bottle for CFS 500mg capsules and 45 in a bottle.. if the best effect was produced on 1000mg 3x a day.. to achieve that 3gram a day dose would i need to buy 4 bottles at $499 for a one month supply? I sure can’t afford that.
that 45 capsule bottle will last 7 days if i take 1000mg 3x a day. this is way too expensive. would be great if somehow there was a large package pricing deal.
any way we can find out what the wholesale pricing” cost is?
what kind of success are folks having at at what doses?
thank you
looks like 1000mg 3x a day for best results ?? is my math right? 1 bottle of the 90 caps will get you through about 14 days of a trial for $500. so a months worth would be $1000. ?? oh my this makes me sad.
“Although the study did not track them, at 1,000 mg 3x’s day, Kaufman stated fatigue improved even more and referred to a 55-year-old man who’d had ME/CFS for 10 years and who received few gains at 500 mg/2x’s a day but whose fatigue plummeted (from 60-20 on the Chalder scale) when he took 1,000 mg/3x’s day.
I wonder if taking it rectally would reduce the amount you gave to take hence making it cheaper.
I wonder where can one find a higher then 100mg OAA dose ? I only know of BenaGene from iHerb and just started taking it today…ironically I felt terribly tired and sleepy in the afternoon ( I didn’t have such a good night but connected 3.5 hrs which for me is great / also noticed I’ve a bit of a cold ) Thanks 🙂
Coincidence? Food for thought… I recently watched a Nextflix documentary called “Diagnosis”. If you watch Season 1, Episode 1, it’s about a 23 yr old female named Angel that suffers from episodes of extreme muscle pain. In the end she is diagnosed with CPT2 (carnitine palmitoyltransferase type 2), which is a gene deficiency. She’s required to lower her fatty acids & increase her sugar.
On the Jubilance website it states: “With just one capsule per day, oxaloacetate helps turn fatty acids into glucose, ensuring that sugar energy is readily available for the cerebellum during PMS”.
More on the cerebellum… https://www.medicinenet.com/what_is_the_main_function_of_the_cerebellum/article.htm Read “What are the signs and symptoms of a cerebellar disorder?” and I think you’ll find many similarities in symptoms. I know that I’ve experienced 5 of the 7 symptoms listed.
Worth noting: I’ve always had a difficult time reducing carbs. Specifically pasta & rice that turn to glucose quickly.
Just take biotin. It converts pyruvate to oxaloacetate via the pyruvate dehydrogenase enzyme pathway, bypassing the more complex pathway which requires B1, B2, B3, and B5 (though the longer pathway also generates acetyl CoA).
Interesting, I will read up on this, thank you.
This is very interesting. Have you tried this? And if so at what dose?
Is there a link to Dr. Kaufman’s study?
No published study yet that I know of’
I just posted a link in my post at the (current) end of this thread. It was published just under a month ago in June 2022. Calling it a study is a real stretch, and the word “controlled” was used loosely. It has an extremely bias-prone design and the vendor has a hand in it rather than independence of researchers from vendors found in legit studies. I’m much more interested in what Dr. Davis and Stanford are researching than some uber-overpriced dietary supplement that has no proof it is even penetrating cell walls. At least the vendor used the word “anecdotally” honestly in the abstract.
PubChem ID is the same for both Benegene original & AOR descriptions of oxaloacetate, and both are synonyms of “oxalaacetic acid”:
Original: anhydrous Enol-Oxaloacetate
AOR: 3-carboxy-3-oxopropanoic acid
So they appear different but may not be…
It takes greater minds than mine…
https://pubchem.ncbi.nlm.nih.gov/compound/970#section=Depositor-Supplied-Synonyms.
You’d better find MSDS or SDS know more about the drug.
My mother’s name is Judy, and she recently began taking Benagene’s Oxaloacetate 500mg:
Oxaloacetate CFS – benaGene
I am very excited to share her recent experience!
Judy has suffered from ME/CFS for 32 years now. I remember her being a dynamic professional woman as well as a piano teacher and a devoted mother. Then after a flu, she developed ME/CFS and never recovered. I would characterize her case as moderate to severe. I have been actively engaged in her health care in my adult years, during which time nothing has worked to make a substantial difference in her health. This includes a multitude of visits to traditional doctors as well as a plethora of supplements and natural health strategies.
So initially, when I was made aware of oxaloacetate from a friend who happened upon recent information about it online, I was skeptical. However, I looked into it and found this article. I was surprised and intrigued. We are aware of Health Rising and familiar with Dr. Kaufman’s involvement with the CFS community. After reading the article and all the helpful comments, unbeknownst to my mom, I felt motivated to purchase a bottle and try this treatment for her.
Judy began taking 2 pills/day (1000mg total) on March 16th. The results were very subtle at first but almost immediately noticeable. She expressed that it was like there was a “substance” to her energy that normally was not there. This “substance” to her energy has slowly but steadily grown day by day. On March 28th she increased the dosage to 3 pills/day (1500mg). What’s most significant is the apparent decline in post-exertional malaise (PEM). She still is weak but recovers faster and doesn’t seem to stay down. Her appetite has increased, she is more active, gets tired at a more normal time, and is sleeping better. It’s incredible to observe these changes and we are excited to see how this develops!
From the bottom of our hearts, we have to give a huge thanks to Cort and Health Rising for making us aware of this opportunity.
How exciting. Thanks so much for sharing :). I love the description of there being more “substance” to her energy. I can relate!
How wonderful to hear. Very glad for your mum. I have just started BenaGene OAA at 100mg per day….Where can one find 200mg and a 500mg dose? Many thanks 🙂
How is your Mom doing with the OA now? Is it still working? If not, how long did it help her? How much did she take? Did you find a less expensive way of buying it?
Any recent news or results from people taking this?
Does it really work other than lightening your wallet significantly? Does it prove P.T. Barnum was timelessly right?
We in the ME/CFS community need to educate ourselves on what constitutes a good scientific study of a supplement or drug, because in our desperation, we become vulnerable to hucksters, including those that wordsmith things like “studied in Alzheimers, cancer, etc., etc.,” or “patented.” At least one of Mr. Cash’s companies, Terra, pushing enol-oxaloacetate, have been warned previously for unsubstantiated claims, so are closely wordsmithing their product now as a “medical food” and trying to legitimize it, but still making suggestions that are, when we read them through our desire for any improvement, claims. You also want to question studies controlled or strongly influenced by the vendor and their employees or consultants. Or when free supplements are made widely available by the vendor to try to get the word on the street.
MetVital is another Cash company pushing the same uber-expensive supplement. There was another one on the past whose name I forgot.
Even in the latest study using Dr. Kaufman’s clients, Mr. Cash uses the word “anecdotally” to describe results in the abstract, to avoid making a claim. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03488-3
It is true that oxaloacetate is present in the Krebs energy cycle. Shortages in vitro are hypothesized at the point, not quantified. However, there is no guarantee if you take these really, really, really expensive pills, that a therapeutic level will arrive outside the cell walls, or that the substance will penetrate the cell in enough quantity to make any difference versus that already produced inside the cell, unlike a real studied drug and not a “medical food.” For uncontrolled studies, placebo effect can be powerful. Do we want to rely on studies with nematodes (worms)? Matter of fact, the Alzheimers study was a dud. All it proved was the drug was not toxic. Endpoint results were withheld.
Do your research. https://psblab.org/?p=618 Be aware of unattributed or untraceable testimonials which can be just as unreliable as Amazon reviews.
Still, if the compound is present in vitro and is not toxic in the quantities taken, it is worth a try apart from affordability. You may be just making expensive urine in the end. But, if apparent claims and wording are artfully created, we, in our desperation, can spend hundreds of magnitudes more than the compound is worth, and a huckster can make a killing off an already financially ravaged community. IMO, that’s what’s being done here, and that makes me, as a ME/CFS sufferer, really angry. Martin Shkreli did this very thing with low volume FDA-approved drugs for orphan diseases. “They’ll pay anything!” Of course Terra/MetVital can afford to give a lot of these pills away free!
Cash’s patent application adds calcium carbonate (same ingredient in Tums) to oxaloacetate to “stabilize” it, then a compatible sweetener, pressing agent, and preservative. So, take a inexpensive substance, add some more cheap substances, put it in a capsule, then charge a rapacious price to a desperate clientele–us! Note how many Pubmed studies are published in part by Terra personnel. This is an “a-ha” indicator. I’m all for innovative drugs or supplements, but like everything else, we need to turn over some stones to find out who’s behind the curtain, what may create biases and corrupt results, and whether there is real science there. The placebo effect and our biases can be powerful.
Note that I use “in vitro” above when I meant “in vivo.” Brain fog…
Fascinating study. I’m based in the uk and have just bought a bottle at huge expense. Have been taking 1500mg for 2 days and seem to be getting worse…it may be to do with dosing or the progression of my illness (have ME and FM), so I can’t attribute my deterioration to OXA.
I don’t want to pour cold water on the study but I do have growing reservations based on the analysis of Paul Rhodes about the limited biochemistry of OXA (a very respected expert in mitochondrial dysfunction):
https://psblab.org/?p=618
I would be interested to see what others make of this…having Cash so closely involved in devising the study and collecting results does seem very problematic to me.
Apologies DaveyME- I didn’t see your blog when I posted mine (perils of posting in a sleep deprived state!). Needless to say, I agree with a lot of what you’re saying. Rhodes doesn’t have any skin in the game either way and his scathing analysis of what OXA can actually do at a biochemical level does really concern me and I’d like to see what other pharmacologists or mitochondrial experts might have to say on the matter. I’d really welcome any update Cort once the proper trial yields results. But unless it’s a double blind placebo I’d be inclined to be very suspicious. False hope esp when you spend so much of your precious savings on a drug like this, is quite damaging. I am also a former patient of Dr Kaufmans and I think he is a really good and kind doctor. I just hope this association with Terrabiologica does not become dominated by their agenda. They should not have any involvement in a future trial if it’s to be credible. These conditions are already tarnished with a reputation for being based on shaky medical science so the airtime given to a food supplement that doesn’t stack up to its claims may well do more harm- I do think that in the age of covid there are almost certainly more people interested in these conditions and any potential treatments. Thanks for your time
Where can I buy oxaloacetate?
I would like to add NADH, Manganese and Benfothiamine to the list of possible enhancers. But not all at once, of course…
Benfothiamine can affect sleep, might be better to only take it before noon…
Oh boy Benagene Oxoalacetate at 500mgs or 200mgs gives me the worst indigestion and gastritis ever. This is the stuff that is thermoregulated and has no Vitamin C.
Have been unable to keep taking it I’m surprised some of the participants didn’t complain about too.
And yes I did take it with food.
Has anyone contacted Jubilance/Benegene about negotiating a lower price for bulk buys? To get 500 mg BID, we would need 10 bottles a month, and lowest subscription price I found was $42 per bottle! Online coupon codes don’t seem to work at either site.
I have seen some modest short term results taking 100 mg BID, but it doesn’t last long enough to affect functional energy, just alertness.