Gerry Gajadharsingh writes:
“I’ve included two different but related pieces of information on this recent research below. Fatigue is a significant symptom with so-called long Covid. There are probably different pathways involved, but the research has flagged up that one is to do with the function of the mitochondria (the so-called powerhouse of the cell) and also coexisting inflammation, so probably not a surprise to many of us.
The therapeutic intervention was with something called AXA1125, which sounds quite scary, but it turns out to be a blend of different amino acids, but at a much higher therapeutic dose, the normally used. So, I’ve included a bit of information from someone who has looked into the preparation previously used by the company manufacturing AXA1125 for NASH (fatty liver), or what we call in the UK non-alcoholic fatty liver disease (NAFLD).
Common energy pathways, include, of course delivery of oxygen on a cellular level, which depends on optimising breathing patterns, something that I’ve blogged about on many occasions before, glucose regulation, balance within the autonomic nervous system, and given that this particular preparation AXA1125 is from amino acids and amino acids are derived from protein, adequate protein intake also seems to be incredibly important. Many patients I see do not have adequate protein intake or a good enough variety of good quality proteins to make sure they are receiving all of the essential amino acids that the body simply cannot make.
Of the main amino acids used in the trial N-Acetyl-Cysteine (or NAC for short), helps to replenish Gluthianone levels (an important antioxidant) in the body, which is part of your liver detoxification pathway and also helps regulate glutamate. Glutamine another of the amino acids used in the product forms glutamate and plays a key role in the citric acid cycle (Energy production cycle within the body).
Inflammation is generally an underlying cause of many disease processes and the best way to manage inflammation from the dietary perspective is eating three balanced meals per day, and not snacking in between meals which pushes up insulin and insulin tends to be pro inflammatory activating other inflammatory cytokines and hormones.”
Medscape
Jay Croft
In a Phase 2 clinical trial of a potential treatment for fatigue associated with long COVID-19, people who received the medicine reported positive results over those receiving a placebo.
The study was conducted by researchers at the University of Oxford and reported in eClinical Medicine.
It was one of the first randomized double-blind placebo-controlled trial for a possible treatment for long COVID, Oxford said in a press release.
“People living with long COVID in the trial who received AXA1125 had a significant improvement in fatigue compared to those who received a placebo,” Oxford said.
Forty-one people participated. They had fatigue for 18 months beforehand. All completed the study, and none reported serious side effects, Oxford said.
AXA1125 was developed by US pharmaceutical company Axcella Therapeutics.
Long COVID refers to persistent symptoms, including fatigue, that last more than 12 weeks after infection. “Potential causes include reduced mitochondrial function and cellular bioenergetics,”the study says.
“AXA1125 was tested in long COVID fatigue as previous data from Axcella showed effects on cellular energetics and inflammation. Emerging data on long COVID suggests that the virus targets the mitochondrial, which are essential to normal energy generation and control of inflammation,” Oxford said. “AXA1125 may improve energy generation and reduce the amount of inflammation in the body.”
The study’s authors wrote that AXA1125 was tied to a “significant reduction in 28-day Chalder Fatigue Questionnaire score relative to placebo.” They said participants who reported less fatigue also had better mitochondrial health and walked farther in a six-minute test.
Sources
eClinical Medicine: “Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study”
CIDRAP: “Experimental metabolic drug cuts fatigue in long-COVID patients”
AXA1125: Amino Acid Formula for Long Covid
Here is the composition, and some things that we know, (and don’t know)
Jonathan Bryon
Oxford University is testing a mix of amino acids that were chosen for the possibility of reducing fatigue and muscle weakness in Long Covid. The formula they are planning on testing was originally developed by a US company and showed some value for NASH (fatty liver).
The formula includes 6 amino acid compounds, and if the research pans out, might provide a safe, cost-effective way, and readily available method to reduce some of the common symptoms that Long Haulers experience.
What is in AXA1125?
Here are the six amino acid compounds and the relative amounts of each in the 6 gram packets that were used in an early study:
- Leucine – 1.00 gram
- Isoleucine: 0.50 gram
- Valine: 0.50 gram
- Arginine: 1.81 grams
- Glutamine: 2.00 grams
- N-Acetyl-Cysteine: 0.15 gram
The first studies on this formula involved pre-packaged envelopes of the powder with an orange flavour; participants were told to mix the powder with water immediately before drinking. The N-Acetyl-Cysteine (NAC) typically has a bit of a sulphurous smell, and when sitting in water, the acetyl group can split off over time and make it even more sulphurous and noxiously sour (acidic). An alternative is to take the NAC separately in capsules and have a 5 amino-acid beverage that is less stinky and more neutral. And the remaining amino acids are more stable and can probably be dissolved in solution for a while.
For the NASH study, subjects consumed 48 grams per day of the amino acid blend… that is 4 packets (6 grams each) dissolved in a glass of water in the morning, 4 packets dissolved in water in the evening.
How much does AXA1125 Cost?
I went online and got the following prices for each amino acid… this is in the United States, for people purchasing small amounts (1-2 pounds at a time):
- Leucine: 4.0 cents per gram
- Isoleucine: 5.8 cents per gram
- Valine: 3.2 cents per gram
- Arginine: 2.6 cents per gram
- Glutamine: 4.4 cents per gram
- N-Acetyl-Cysteine (NAC): 16.8 cents per gram
(Note: the NAC seemed to be in short supply and is noticeably more expensive than when I bought some a year or two ago – many people are taking it for covid concerns. Even though there are many different companies that package it for sale, most of the raw product comes from a small number of bulk manufacturers and production has not expanded enough to meet demand and keep prices of NAC low.)
If we calculate the weighted average cost for the mixture, 1 gram of mix-it-yourself generic AXA1125 is around 4.1 cents. If the standard dose is 48 grams per day, that translates to just under $2 per day.
A price of $60 per month is not particularly cheap, but if a person has significant impairment and this cocktail of amino acids alleviates some of the fatigue and lets a person live a more normal life, it could be worth it. (At this time, there isn’t evidence to say whether this helps people or not.)
Although the cost of a daily dose of AXA1125 is relatively modest, it is not cheap. If you are going to blend it yourself, you are going to have to buy in bulk, and the initial layout to get a supply costs around $120 upfront
Because some amino acids make up a big part of the formula and others are used in much smaller amounts, the DIY mixologist will have to re-order different aminos at different times to keep the stock replenished if they continue taking this supplement. If a person takes the blend daily for many months, the cost will average out to $60 per month, but the required purchases will not be evenly spaced. Put in other terms: this costs $720 a year.
As I understand it, the company sponsoring the research (Axcella) might be seeking intellectual property protection on the use of this blend of amino acids for commercial purposes. This might create an issue for anyone who tries to sell the amino acids in that particular ratio, or who makes claims while selling such a blend. It does not prevent a person from taking amino acids for their own health. In a similar way, there are patents on the use of highly purified fish oils for treating cholesterol and triglyceride levels in people with heart disease, but it is also still possible to buy generic fish oil and take it for whatever purposes a person wishes.