R Lipoic Acid vs Alpha Lipoic Acid?

Pyrrhus

Senior Member
Messages
2,913
Likes
8,511
Location
U.S., Earth
Regular alpha-lipoic acid (ALA) is a racemic mixture of R-ALA and S-ALA. Only R-ALA is naturally found in the human body. There is some evidence that S-ALA may be harmful. Therefore, some people prefer to take R-ALA instead of regular ALA, which is a mixture of R-ALA with S-ALA.

Hope this helps.
 
Last edited:

pamojja

Senior Member
Messages
2,293
Likes
3,323
Location
Austria
All clinical trials showing benefit from lipoic acid were with regular lipoic acid. Since it contains also half of R-ALA, and the price of R-ALA isn't even by far half that of usual, I've using regular only. Couldn't afford otherwise.

There is some evidence that L-ALA may be harmful.
Would you be so kind to provide links?
 

Pyrrhus

Senior Member
Messages
2,913
Likes
8,511
Location
U.S., Earth
All clinical trials showing benefit from lipoic acid were with regular lipoic acid. Since it contains also half of R-ALA, and the price of R-ALA isn't even by far half that of usual, I've using regular only. Couldn't afford otherwise.
Would you be so kind to provide links?
There was a study from the 1960's that found that very high-dose S-ALA was toxic when administered to thiamine-deficient rats:
https://www.nature.com/articles/207535a0.pdf

A 1997 study found that S-ALA increases insulin in diabetic rats, while R-ALA decreases insulin in diabetic rats:
https://journals.physiology.org/doi/abs/10.1152/ajpendo.1997.273.1.E185

Overall, the evidence for harmful effects of S-ALA is rather weak, though.

Hope this helps.
 

pamojja

Senior Member
Messages
2,293
Likes
3,323
Location
Austria
Overall, the evidence for harmful effects of S-ALA is rather weak, though.

Hope this helps.
Thanks, wasn't aware of.

And true, such tiny concerns in both cases of rats and ALA intraperitoneally injected, and not replicated in human studies isn't a concern for me. Now I saw the review of ALA at https://lpi.oregonstate.edu/mic/dietary-factors/lipoic-acid#supplements only mentions 1 study, where also intraperitoneally injected ALA in rats actually improved glucose metabolism.

Supplements

Unlike lipoic acid in foods, lipoic acid in supplements is not bound to protein. Moreover, the amounts of lipoic acid available in dietary supplements (50-600 mg) are likely as much as 1,000 times greater than the amounts that could be obtained from the diet. In Germany, lipoic acid is approved for the treatment of diabetic neuropathies and is available by prescription (108). Lipoic acid is available as a dietary supplement without a prescription in the US. Most lipoic acid supplements contain a racemic mixture of R-lipoic acid and S-lipoic acid (sometimes noted d,l-lipoic acid). Supplements that claim to contain only R-lipoic acid are usually more expensive, and information regarding their purity is not publicly available (109). Since taking lipoic acid with a meal decreases its bioavailability, it is generally recommended that lipoic acid be taken 30 min prior to a meal (see also Metabolism and Bioavailability) (8).

Racemic mixture versus R-lipoic acid only

R-lipoic acid is the isomer that is synthesized by plants and animals and functions as a cofactor for mitochondrial enzymes in its protein-bound form (see Biological Activities). Direct comparisons of the bioavailability of the oral racemic mixture and R-lipoic acid supplements have not been published. Following the ingestion of R,S-lipoic acid, peak plasma concentrations of R-lipoic acid were found to be 40%-50% higher than S-lipoic acid, suggesting better absorption of R-lipoic acid. Both isomers were nonetheless rapidly metabolized and eliminated (6, 8, 11). In rats, R-lipoic acid was more effective than S-lipoic acid in enhancing insulin-stimulated glucose transport and metabolism in skeletal muscle (110), and R-lipoic acid was more effective than R,S-lipoic acid and S-lipoic acid in preventing cataracts (111). However, all of the published human studies have used R,S-lipoic acid (racemic mixture). It has been suggested that the presence of S-lipoic acid in the racemic mixture may limit the polymerization of R-lipoic acid and enhance its bioavailability (52). At present, it remains unclear which supplemental form is best to use in clinical trials.
Wasn't aware it might be better taken before a meal.

Safety
Adverse effects

In general, high-dose lipoic acid administration has been found to have few serious side effects. Intravenous administration of lipoic acid at doses of 600 mg/day for three weeks (112) and oral lipoic acid at doses as high as 1,800 mg/day for six months (113) and 1,200 mg/day for two years (76) did not result in serious adverse effects when used to treat diabetic peripheral neuropathy. There was no significant difference in the incidence of adverse events and serious adverse events in patients with diabetic neuropathy who took 600 mg/day of lipoic acid for four years compared to those in the placebo group (78). Oral intake of 2,400 mg/day for two weeks was also found to be safe in a pilot study that included participants with multiple sclerosis (95). Two mild anaphylactoid reactions and one severe anaphylactic reaction, including laryngospasm, were reported after intravenous lipoic acid administration (55). The most frequently reported side effects of oral lipoic acid supplementation are allergic reactions affecting the skin, including rashes, hives, and itching. Abdominal pain, nausea, vomiting, diarrhea, and vertigo have also been reported, and one trial found that the incidence of nausea, vomiting, and vertigo was dose-dependent (77). Further, malodorous urine has been noted by people taking 1,200 mg/day of lipoic acid orally (95).
Instead of thiamine, only a possible biotin-interaction mentioned:

Nutrient interactions
Biotin


The chemical structure of biotin is similar to that of lipoic acid, and there is some evidence that high concentrations of lipoic acid can compete with biotin for transport across cell membranes (120, 121). The administration of high doses of lipoic acid by injection to rats decreased the activity of two biotin-dependent enzymes by about 30%-35% (122), but it is not known whether oral or intravenous lipoic acid supplementation substantially increases the requirement for biotin in humans (123).
 
Last edited:

pamojja

Senior Member
Messages
2,293
Likes
3,323
Location
Austria
So in your case 100 mg of R-ALA gave better results than 600 mg of mixed ALA. That's quite a significant difference.

What other detox-methods addtional to ALA? Which might also be a influencing factor, compared to only taking ALA not particularly for detox.
 

LINE

Senior Member
Messages
361
Likes
735
Location
USA
That is a good question concerning the differences. My experiments are not fool proof, but I think that was the case. Could be a difference in the formulation.

For detox, I add other things including Pascalite clay (used Zeolite resultsrna spray for quite some time). I like to put it under the tongue with a little water and let it sit. The rationale behind this is systemic absorption. It can also be ingested so it gets to the gut. . The clays are excellent for detox.

I also use Clean Chlorella which in testing has proved to be less contaminated than other versions. He has the testing to show this. I used other forms previous to this. I also use bulk charcoal for many years. And maybe once per week, do oral EDTA (2 caps).

I also support liver detox with milk thistle type of products and support methlylation with a mix of b vitamins, sulfur containing amino acids such methionine, taurine and NAC or cysteine. I also use sunflower lecithin which contains phosphatidylcholine which is supportive of both liver and cell membranes.
 

LINE

Senior Member
Messages
361
Likes
735
Location
USA
So in your case 100 mg of R-ALA gave better results than 600 mg of mixed ALA. That's quite a significant difference.

What other detox-methods addtional to ALA? Which might also be a influencing factor, compared to only taking ALA not particularly for detox.
New experiment, rLipoic works better than the ALA/RLA combination. rLA = 100mg, ALA/rLA is 600mg.
 

Pyrrhus

Senior Member
Messages
2,913
Likes
8,511
Location
U.S., Earth
So in your case 100 mg of R-ALA gave better results than 600 mg of mixed ALA. That's quite a significant difference.
New experiment, rLipoic works better than the ALA/RLA combination. rLA = 100mg, ALA/rLA is 600mg.
Thanks for reporting the results of your experiments. Is your R-ALA the sodium salt (Na-R-ALA) or some other formulation of R-ALA?

I ask because it has been reported that the sodium salt (Na-R-ALA) is roughly three times as bioavailable as straight R-ALA.[1] This is attributed to the fact that straight R-ALA can polymerize and clump together instead of being absorbed. This same report claimed that:
Reference 1 said:
RLA in a salt form is considerably more bioavailable than an equivalent dose of [mixed racemic] LA (RLA + SLA). This indicates SLA may function as a competitive inhibitor in the absorption of RLA.
Reference
[1] http://archive.foundationalmedicinereview.com/publications/12/4/343.pdf
 

LINE

Senior Member
Messages
361
Likes
735
Location
USA
Yes, it is Doctor's Best Stabilized r-Lipoic with Bioenhanced NA-RALA.

I have a friend with ME stuff going on and has lesions breaking out on her skin, I have attempted every way to detox (some sophisticated approaches) which has not worked (and caused some short-lived problems), but this product seems to give her some relief after a short period of time. I believe that once the cells start normal or semi-normal functioning, then things should get back to center. Of course, she is doing a wide array of antioxidants and other dense nutritionals which keep her afloat. It has been my experience that if I cannot detox properly, I got worse. Keeping a robust detox program, keeps me above water.

If you research pyruvate dehyrdogenase (PDH), you will see that this is an intermediate within the Kreb's cycle and is an important component of that cycle. CFS research shows that PDH is inhibited in CFS patients, the author makes the claim that PDH is inhibited by infections. https://insight.jci.org/articles/view/89376

Dr. Fluge is a known M.E. researcher and had this to say about PDH impairment:

"I think that at present our data are primarily telling us something about the ME/CFS disease. Our findings indicate an impaired function of the PDH enzyme complex, resulting in reduced flux of pyruvate to the [tricarboxylic acid (TCA)] cycle. Increased lactic acid accumulates upon limited exertion, and there is a compensatory use of alternative substrates to fuel the TCA cycle. So, the results indicate an impaired mitochondrial PDH complex function, we believe induced by the immune system,"


If PDH is blocked then energy cannot be produced in the cell, thus leaving the cell with compromised vitality. As you know, the cells do stuff like detoxify, create immunity etc. I would also note that PDH problems induces neurological problems which ME patients seem to have.

From Wikipedia:
Enzymatic activity[edit]
Lipoic acid is a cofactor for at least five enzyme systems.[3] Two of these are in the citric acid cycle through which many organisms turn nutrients into energy. Lipoylated enzymes have lipoic acid attached to them covalently. The lipoyl group transfers acyl groups in 2-oxoacid dehydrogenase complexes, and methylamine group in the glycine cleavage complex or glycine dehydrogenase.[3]

2-Oxoacid dehydrogenase transfer reactions occur by a similar mechanism in:


Sorry for the long post
 

Pyrrhus

Senior Member
Messages
2,913
Likes
8,511
Location
U.S., Earth
Lipoic acid is a cofactor for at least five enzyme systems.[3] Two of these are in the citric acid cycle through which many organisms turn nutrients into energy. Lipoylated enzymes have lipoic acid attached to them covalently. The lipoyl group transfers acyl groups in 2-oxoacid dehydrogenase complexes, and methylamine group in the glycine cleavage complex or glycine dehydrogenase.[3]
Thanks, I enjoyed your long post. I will add one more bit from Wikipedia:
Wikipedia page on Lipoic acid said:
As a result, lipoic acid is synthesized attached to proteins and no free lipoic acid is produced. Lipoic acid can be removed whenever proteins are degraded and by action of the enzyme lipoamidase.[8] Free [lipoic acid] can be used by some organisms [by using] an enzyme called lipoate protein ligase that attaches it covalently to the correct protein.
I think this raises an important, but overlooked point. Alpha-lipoic-acid (ALA) in its natural state in the mitochondria only exists bound to protein. There is no free ALA naturally floating around in the human body. So when we ingest free ALA, the effects we see could be due to free ALA floating around in the body, or the effects we see could be due to mitochondria that have managed to bind the ALA to the correct protein in the mitochondria.

When I looked through the literature describing the mechanism of action of ALA supplements, the articles mostly tended to assume that the effect of ALA supplements is due to free ALA floating around in the body.[1] Indeed, that is the same assumption made by chelation protocols that call for ALA in order to remove heavy metals.

But the literature also included a number of ALA trials that implied that ALA supplements improve mitochondrial function, which then implies that free ALA may sometimes end up bound to the correct protein in mitochondria.[2] I have tried to elucidate the enzymatic steps that would need to occur for this to happen:
  1. Free ALA is first activated by enzyme ACSM1
  2. Activated ALA is then bound to the correct protein in the mitochondria by enzyme LIPT1
However, despite ample clinical evidence that ALA improves mitochondrial function, it has never been directly proven that free ALA can be correctly bound to the correct protein in mitochondria!

References:
[1] https://www.tandfonline.com/doi/pdf/10.1179/135100005X21624
[2] https://pdfs.semanticscholar.org/be92/f5ec1e2915508fdc146be4eff2e2413cc534.pdf
 
Messages
58
Likes
61
@LINE I'm curious about the Pascalite clay. On this site's page their analysis states it contains 16% aluminum.https://www.pascalite.net/Natural-Wound-Care-Worland-WY.html I believe that is even higher than zeolite. IIRC the debate with zeolite is that it removes more aluminum than it deposits or maybe they state it doesn't deposit any - I can't remember. As I type this I do wonder if the nano-zeolite products (like ResultsRNA) could actually be more dangerous than the larger particle size? I suppose there is a place to use several different sizes of zeolite. Anyway, I'm curious about the Pascalite. I haven't heard of it before. Would appreciate your thoughts on the aluminum content.
I'm pretty sure I'm toxic with heavy metals and would imagine some have passed the bbb. I've been tweaking my B's (that's been a journey), and have been doing Mercola's chlorella, and trying to find a tolerable dose of NAC. (NAC is giving me a headache either due to increased NO, and/or glutamate activity, and/or vasodilation). Have added in zeolite and charcoal. I'm thinking to stay the course for a month or two and then use the more expensive ResultsRNA product you mentioned. Maybe I'll rotate in the Pascalite. I like the idea that it is negatively charged, but am concerned on the aluminum. I drink a lot of Fiji water which removes aluminum - and this may be helpful for keeping aluminum at bay with pascalite.

Regarding ALA. I'm no expert but for those interested I believe this Geronova not only manufactures the most bio-avaible Na-R-LA product, but they have great info on their site. From what I've learned, most people are throwing money away on ALA sups. The R is definitely better and safer, but it loses it potency very quickly on the shelf. I recently did 7 days of 500mg IV ALA (trying to reverse damage done by exceedingly high methylmalonic acid levels). Now, I've switched to Geronova's product and I feel it is just as good as IV. Plus it doesn't contain the S form which is 50% of the IV formula. They happen to sell their LA in bulk which makes it reasonably priced and without fillers and other garbage. https://geronova.com/

The have a new research product called PNB alpha phenyl-N- tert butyl nitrone which is most commonly used for a spin trap. I thought I'd try it, but I think it must cause vasodilation because it (also) increased my headache. But it might be interesting for some folks here to try.
 
Last edited:

LINE

Senior Member
Messages
361
Likes
735
Location
USA
I have excellent results with the bioavailable rLipoic. Definitely a difference from the ala/rla product I was taking. Now I do 1 cap every other day. I have reduced pain, better energy. I mostly gauge products from observation.

I have read the same information on the aluminum content of these products, both the pro and con. I have used resultsrna for over 10 years. Pascalite, I have used 5 bottles. I will remark that I do mineral analysis via hair* and got a positive for cadmium release after I did the resultsrna zeolite. They used to have documentation on their site showing levels on hair tissue analysis. The issue with hair analysis is that heavy metals usually do not show up unless they are 1/ being provoked or 2/ recent exposure. I have not seem any aluminum levels on the hair tests, perhaps I am missing something.

This is a big issue with heavy metal stores, that is that the body will sequester toxic metals, e.g. they go in hiding unless provoked. There is considerable studies showing the agonist/antagonist relationships with normal minerals and toxic metals. In other words, abnormal levels of common minerals can allow the body to put the toxins in storage rather than excreting them. This link shows antagonisms of zinc which include Lead (pb) and Cadmium (cd) https://traceelements.com/Docs/The Nutritional Relationships of Zinc.pdf. Selenium will work against mercury (hg), cadmium (cd) etc. https://traceelements.com/Docs/The Nutritional Relationships of Selenium.pdf

There are other educational articles on that site which are worth reading.

I really like Clean Chlorella which was much better than common chlorella. The argument is that chlorella can collect the toxins if grown in toxic environments. CC claims that their products are grown indoor and not exposed to unnecessary toxins.

I also use small amounts of oral EDTA. Probably an average of 3 to 4 caps per week.

*I use Trace Elements Inc for testing, which I have done for 25 years. I like their approach and educational materials that are provided with their reports. I am a provider as well.
 
Last edited: