R Lipoic Acid – The Different Forms of Lipoic Acid, And Why You Should Care!

R-Lipoic Acid:  

Is there even a difference between the ​forms of lipoic acid on the market?  ​Which Form Should You Take?  Which One Is Wasting Your Money? Which One Could Be Harming You?

I found this in depth presentation randomly searching for resources on ALA (alpha ​ lipoic acid).  

We've been taking ​alpha lipoic acid on and off for a couple years and have not seen any of the results promised.  And yet, just because "you never know" and "studies show it's helpful," we kept ordering and taking it ​- an expensive and potentially damaging practice. 

After watching this presentation by David Carlson of Geronova, I understand what we've been doing wrong and how to fix it.  His presentation has helped me see a path to ​the benefits of alpha lipoic acid.  It's deepened my understanding and knowledge and helped me answer,"Which form and brand will deliver the benefits alpha lipoic acid has to offer?"

What ​Is the ​Difference ​Between ​Alpha ​Lipoic ​Acid and R-Lipoic ​Acid?

Alpha lipoic acid exists as two separate compounds: 

  • R-Lipoic acid, the form that is found in nature and foods.  
  • S-​Lipoic acid, one of the forms created when alpha lipoic acid is produced outside of nature.  

​When mixed together, these two forms are known as Racemic Alpha ​Lipoic​ Acid.  This is what is​most widely sold as alpha lipoic acid.  It's a mixture of R-Lipoic acid and S-​Lipoic acid usually in a 1:1 ratio. 

dr danielle lipoic acid

​Racemic​ ​Lipoic ​Acid, is cheap to produce and widely available.   However, it has been shown to be ineffective at best, and ​potentially damaging at worst.  ​

How Did Alpha Lipoic Acid Supplements Come Into Being?

Alpha lipoic acid was first isolated in 1951.

​Lester Reed at the University of Texas took nearly ten tons of beef liver to produce 30 mgs of alpha lipoic acid. 

Yikes!

Lipioc Acid From Beef Liver

Three years later, ​scientists were able to split the manufactured alpha lipoic acid ​into two components: the natural (R-Lipoic form) and unnatural (S-Lipoic form).

R-Lipoic Acid is produced in the body.  It's in every cell.  It's production in the body declines with age.  Hence it is the form found in nature.  

S-Lipoic acid only exists when lipoic acid is generated... by humans... in labs.

It took another couple years for ​lipoic acid to generate excitement when it was discovered that it ​blocked and reversed the damaging effects of toxic compounds injected into mice. 

Through the late 1950's and into the 1960's, further experiments with alpha lipoic acid's two components showed that the "natural" and "unnatural" forms had different effects. 

R-Lipoic Acid Prevented the Rats From Dying From Arsenic Poisoning.  S-Alpha Lipoic Acid DID NOT! 

R-Lipoic acid, the "natural" component, blocked rats from dying when they had arsenic injected into their hearts.  

S-alpha lipoic acid, the "unnatural" component did not.  

R lipoic acid anti aging

​It was also apparently discovered that rats supplemented with S-alpha lipoic acid had a higher rate of mortality.  This was not the case with the R-form. 

In 1959, alpha lipoic acid was shown to act as an anti-oxidant.  (Both the R and S forms show anti-oxidant effects).

R-Lipoic Acid For Diabetic Neuropathy

In 1966 it was approved for use for the treatment of diabetic neuropathy.

In 1978, alpha lipoic acid's anti-inflammatory properties were discovered.  Only the R-form is anti-inflammatory.

In 1985, they began commercial development of alpha lipoic acid.

R-Lipoic Acid Protects Against Radiation Poisoning

In 1986, they found that giving alpha lipoic acid in conjunction with vitamin E, lead to less damage from the radiation of the Chernobyl disaster.

R-Lipoic Acid Is Anti-Aging

In 1999, the famous rejuvenation experiments took place at UC Berkley. 

Bruce Ames and Tory Hagen ​gave older rats a combination of R-Lipoic acid and acetylcarnitine. (1)  This combination reduced brain markers of oxidation, increased the energy and activity levels of the rats, and "charged" the rats up.  In comparison to their non-supplemented peers, the ​R-lipoic acid and acetylcarnitine rats were said to have "danced the macarena." 

lipoic acid anti-aging benefits

In 2000, Richard Kaufman and David Carlson figured out how to make R-Lipoic acid in the lab and scale up production.  It was also at this time, that alpha lipoic acid supplements hit the market in a big way. 

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What Is the Difference Between R-Lipoic Acid and S-​Lipoic Acid?  What Form Is the Best To Take?

​Alpha lipoic acid has​ many benefits across multiple systems in the body.  And it is, according to Mr. Carlson, that R-Lipoic acid ​deserves the most credit for producing the positive effects that alpha lipoic acid is known for. ​

​​It is here that Mr. Carlson shows a slide that has the two molecules, the R form and the S form of alpha lipoic acid.   ​R-lipoic acid and S-lipoic acid are enantiomers, meaning mirror images of each other.

Lipoic Acid enantiomers

This is what, he suggests, has lead many to claim that​ R-Lipoic Acid and S-Lipoic Acid are interchangeable.  

​But this isn't the case.  These two forms of Lipoic Acid are NOT THE SAME.   ​Cells and proteins in the body recognize and respond to either one form or the other differently. 

For example, R-Lipoic acid has anti-inflammatory effects.  The S-form does not. But the cells will take either form up.  So if the S-form is taken up, the R-form ​isn't. ​ 

In this instance, the S-​lipoic acid will block the positive effects of R-Lipoic acid.   This is known as competitive inhibition.  The S-form inhibits the R-form from being taken up and working.

r-lipoic acid blocked by s-lipoic acid

This is how you can find yourself taking alpha lipoic acid without experiencing any of the claimed positive effects.  

Not sure if you've been in this position.  But we sure have.  You're swallowing pills that you have researched for their effect for whatever - and yet you don't feel or see any difference. 

Mr. Carlson goes on to explain,

​"The enzymes in our body are built to recognize the R-form because it's found in nature. Remember if we go back to the simplest organisms on this planet all of their cells use only that form.   They only reason that the S-form is even out there is because it's cheap and it's easy to make. "  

In addition to S-​lipoic acid competitively inhibiting the R form's ability to bind with proteins, S-​lipoic acid may also cause negative effects.

For example, S-lipoic acid has been found to increase glycosylated hemoglobin (per Dr. Heinz Ulrich).  When this marker is elevated, it indicates poorly controlled diabetes.  ​S-lipoic acid ​also increased increase mortality in rats.  It reduced membrane fluidity and caused cells to become more rigid.  In high doses, S-alpha lipoic acid inhibited mitochondrial metabolism.

So when the S form is combined with the R form into racemic alpha lipoic acid, the one most commonly sold as alpha lipoic acid, its not inert.  It is ​potentially active in blocking many of the positive effects of ​R-Lipoic acid, as well as enacting some additional negative effects of its own. 

*If this is indeed true, this is HUGE - Taking a supplement that contains S-lipoic form is not only not going to have a positive effect, but it has been found to actually  have a negative. 

 Lipoic Acid Does More Harm Than Good

We put a good chunk of change into supplements - and so even beyond the money spent on supplements that may or may not work​, to put money into supps that could be having negative effects is awful.

​R-Lipoic Acid - Clearly the Best Form of Lipoic

​All of this points to R-Lipoic acid as being the ​best form to take. 

Well it's not ​so easy - just yet.   ​

R-Lipoic Acid Has Bio-​Availability Issues 

​When R-Lipoic Acid was studied​, there was apparently a huge gap between its effects in animal models and humans.  Many of the animal trials were conducted with lipoic acid given intravenously or somehow injected into the animals.  Humans primarily take it orally.

It's around this point that science began to realize R-Lipoic acid was extremely unstable and not very bio-available when administered orally. 

Mr. Carlson states,

​"...by the time you get this stuff into a capsule and you swallow it, it essentially has no bio-availability."

​R-Lipoic aicd polymerizes into a sticky chain that is not available to the body.

Essentially, one molecule grabs onto the next one... and so on.... It goes from a crystal formation to a "polymeric mass" that is completely sticky and insoluble.  In this form, the body cannot do anything with it. This is ​what happens inside your gut, when you swallow it.  Its bio-availabilty is very low.

Stabilized R-Lipoic Acid Enhances Bio-Availability

​Carlson's goals were to stabilize R-Lipoic acid and enhance its bio-availability.

His first innovation involved converting it to a salt form to increase its bio-availability.  Sodium R-Lipoic Acid (Na RLA) came to be.

His second innovation used dihydro​lipoic acid, alpha lipoic acid's reduced form. 

On its own dihydro​lipoic acid is also unstable.  However, when it's mixed with R-lipoic, the two together become more stable and soluble - a seemingly win-win situation.

​Dihydrolipoic acid oxidizes inside the body into alpha lipoic acid AND it appears to act as a delivery system for R-lipoic acid​, enhancing bio-availability.

When and How to Take R-Lipoic Acid 

  • ​Take it with ​acetyl-l-carnitine
  • ​Take it with fats like fish oils

​Mr. Carlson then goes onto speak of how the addition of ​acetyl-l-carnitine to R-Lipoic acid ​decreases the active dose requirements:  from something like 10 micromolar down to 1 micromolar.   

*If you read the rejuvenation studies Ames did on rats using R-Lipoic acid, you'll see that he co-administered ​​​acetyl-l-carnitine. (1)

Additionally, he mentions that it's been found that taking ​lipoic acid with fats (like fish oils) increase the lipoic acid metabolite that ​is detectable in the blood.  

In ​a study that he cites, ​an individual ate fat about 30 minutes after taking lipoic acid.  This caused the liver to release​ lipoic acid metabolite into circulation.  This metabolite is believed to have many of the beneficial effects found in alpha lipoic acid.

Misconceptions about Alpha lipoic acid  

Misconception 1:  You Can Get Enough Alpha Lipoic Acid in Food.

This simply isn't true. 

Even though small doses of alpha lipoic acid can be effective, doses as low as 5mg/kg.  This would ​require a 120lb person to get 250mg of alpha lipoic acid as a minimum dose. 

In order to get 250mgs of alpha lipoic acid from food, this person would need to consume nearly 2100 pounds of spinach or 6000 pounds of broccoli. 

alpha lipoic acid in food

You simply cannot get enough alpha lipoic acid from food to get any therapeutic effects.

Misconception 2 - "Healthy people don't need to take alpha lipoic acid." Or if they do, the recommended doses are below effective, like 10-50mg.

​Here Mr. Carlson states, "Does anybody know anybody that's totally healthy?" 

Good point.  

I would add.  

"Does anyone know anyone who is not aging?"  ​ Maybe "healthy" people don't need to take alpha lipoic acid; but anyone interested in anti-aging may want to, even if they are "healthy."

r lipoic acid slows aging
​Misconception  3 - All forms of alpha lipoic acid are the same.

​"The R-Lipoic acid, S-Alpha lipoic acid, and Racemic forms (mixture of R & A) are THREE "pharmacologically distinct. compounds."  They act on the body in very different ways.  There are similarities, yes.  But there are known differences.  

For example, S-alpha lipoic acid actually inhibits the anti-inflammatory effects of R-form through competitive inhibition. 

In the capacity of scavenging free radicals in the blood (which your plasma reveals your true age), the R-form and S-form are equally effective.

However in the case of specific interactions with enzymes, the R form is preferred.

Controlled Release Lipoic Acid VS Quick Release Lipoic Acid

​Normally ​lipoic acid gets into your blood stream within 30 minutes to an hour after ingestion, reaching its peak in that time as well.  It then drops back down to baseline in about three hours.  

​Certain lipoic acid brands​ promote the concept of extending the benefits of alpha lipoic acid by extending the duration of blood levels.

While this is a good idea, it doesn't have any tests behind it to prove or disprove it. And the opposite might be true.​  That is "shocking the system with a high dose and concentration quickly" may cause more benefits. (3)

Measuring the Blood Levels to See Changes in Markers

Mr. Carlson discusses​ th​e benefits of using blood markers as indicators of whether or not a supplement is effective. 

I like this approach.  In my research for supplements to add to our regimen, I'm always looking for ​studies that have blood levels of IL-10, IL-12, IFN-gamma... behind them. 

He goes on to discuss studies that he and his team performed on themselves ​using different dosages of R-lipoic acid and subsequent blood ​tests.  ​ 

He cites a study where participants were given 1 gram of R-Lipoic, which raised blood levels 24 times that of the baseline level.  In comparsion the study that Mr. Carlson and his team ran using their proprietary R-Lipoic acid yielded 111 times baseline blood levels using a 600mg dose.

R-Lipoic Acid Benefits 

R-Lipoic Acid has many scientifically-backed benefits for cardio-vascular function, immune system stimulation & modulation, energy production, neurological and brain function, liver function & protection, kidney function, metabolism, diabetes and anti-aging. 

  • R-Lipoic acid when taken up by cells affects ion channels, calcium uptake, sodium uptake, interferon-gamma receptors...thereby it has the ability to alter gene transcription. 
  • R-Lipoic acid effects insulin signaling.  This has therapeutic use in diabetes.  Not to mention that it has been found to alleviate diabetic neuropathy.
  • R-Lipoic acid has been shown to block a protein associated with cellular apoptosis.  While apoptosis is necessary for clearing damaged cells and tissues, in aging cells undergo apoptosis faster than they are replaced.  lipioc acid can block some of that.
  • R-Lipoic acid reduces inflammation induced damage to vascular endothelial cells, which benefits cardio vascular function and health.
  • R-Lipoic acid plays important roles inside of the mitochondria.
  • R-Lipoic acid supplementation increases energy.
  • R-Lipoic acid has anti-oxidant functions.  It's also able to chelate toxins and heavy metals.
  • R-Lipoic acid shows the capacity to control atherosclerosis through increasing vasodilation and reducing the blood cell stickiness that causes vascular damage.
  • R-lipioc acid reduces inflammatory cytokines like tumor necrosis factor and IL-6.
  • R-Lipoic acid improves glucose uptake.
  • R-Lipoic acid can reverse age-related "the age-related association in the thiol status as we age," in the blood and tissues.
  • R-Lipoic acid increases glutathione levels.
  • R-Lipoic acid reduces IgE levels and skews the immune system towards Th1. (2)

​​"Since people have measured the redux state of the blood and have correlated that to aging I think that the blood should actually be considered a therapeutic target instead of only thinking of it as a means of delivering it to the tissues organs."

Benefits of R-Lipoic Acid Extend to the Blood Itself

R-Lipoic acid can effect activities in the blood and therefore cytokines, red blood cell flexibility, it can prevent blood cells from getting blocked in the capillary beds, and most importantly, it can reduce inflammation in the vascular endothelia.  This is huge because cardiovascular disease and atherosclerosis are major causes of death across the planet.

​R-lipoic ​acid ​also effects ​levels of cysteine, homocysteine, and other aminothiols in the blood.  For something like cysteine, it's oxidation levels increase with age after 18.  If you can effect that, you can potentially slow or reverse of the aging process.

​Beyond just acting as an anti-oxidant, r-lipoic acid ​acts on certain genes and organs in an anti-aging capacity​ that is comparable to caloric restriction.  (4)

Exciting Research On the Benefits of Alpha Lipoic Acid

​Using ​alpha lipoic acid ​for treatment of metabolic syndrome is another hotbed of current and upcoming research.

​R-lipoic acid appears to generate cellular energy through a protein called AMPK (metabolic master switch ​and appetite suppressor).  ​Pharma is investing money into AMPK-stimulating drugs.  But, R-lipoic may do the trick.  (5)

R-lipoic appears to increase AMPK levels in muscles (boosting energy), while decreasing AMPK in the hypothalamus (causes sensation of satiety).  ​

Studies using R-lipoic to stimulate AMPK in weightloss have seen results that include:

  •             Increaced glycemic control
  •             Increased lean muscle mass
  •             Decreased fat accumulation
  •             Decreased LDL

Results have been similar to using metformin, which also stimulates AMPK.

The mechanism through which R-lipoic does this is still unknown.  Further research resources need to be applied there.

R-Lipoic Acid Stimulates & Reactivates ​Protective Genes

Tory Hagen, at LInus Pauling Institute, recently published a paper that shows that R-lipoic stimulates and activates NRF2. (6)

NRF2 is a transcription factor that activates over 200 defense genes that decrease in activity as we age.   R-Lipoic acid appears to up regulate or reactivate these protective genes.

*Tory Hagen also most recently ​published around restoring normal circadian function in aging humans using R-lipoic acid. (7)

​Almost one-third of all genes are influenced by circadian rhythms, and when out of balance they can play roles in cancer, heart disease, inflammation, hormonal imbalance and many other areas, the OSU researchers said." ​

​Tory Hagen

R-Lipoic Acid As a Defense Against Viruses

Mr. Carlson then goes on to discuss H5N1 and the inevitable pandemics that may hit the US over the next couple decades.  The main cause of death in H5N1 is the cytokine storm.  Basically the immune system overreacts and over-releases a chemical cascade that ​overwhelms the person and leads to death.

He suggests that alpha lipoic acid may be able to control this cytokine storm in people who may be prone to have over reactive immune systems. 

Alpha Lipoic Acid Dosages For Weightloss and Energy

alpha lipoic acid weightloss

​Then Mr. Carlson goes on to discuss effective doses for different effects.  

He mentions that for weight-loss, most people take between 700-800mg/day. Although here is study where overweight women lost 35% more weight when supplemented with lipoic acid, than their un-supplemented counterparts.  ​The women were given 100mg capsules with each meal, for a total of 300mg/day.   (8)

The lipoic acid the study used was racemic.  Here is the brand they used.

Although given what I've now learned about about R-lipoic acid vs racemic alpha lipoic acid, I wonder if the women in the study may have lost more weight using the R-lipoic form?

​Per Mr. Carlson, most people experience better energy around 300-400mg/day.  A minimum would be 5mg/kg.

​Alpha Lipoic Acid Best Brand

​Alpha Lipoic Acid Best Brand

With all the points that Mr. Carlson makes, it's easy to see how most of the alpha lipoic acid products on the market ​may be ineffective, or potentially damaging. This is unfortunate, especially given that alpha lipoic acid supplements can be expensive.

Mr. Carlson also goes on to comment on claims made by alpha lipoic acid brands.... claims which are patently untrue and misleading.  His company tests samples that claim to be R-Lipoic acid, but are not.  He says that most companies are not testing their materials.  They just put the stuff in a pill and sell it. 

Ugh!

​Best Lipoic Acid Brand - The Biggest Bang for Your Buck!

​I highly recommend that you watch David Carlson's presentation and see what you think.   He inspired me to reevaluate the lipoic acid we were taking, Pure Encapsulations Alpha Lipoic Acid.

They also sell an R-lipoic acid that is "stabilized."  However, it's not Na-RALA (at least that's not what they label it as) and it's super pricey in comparison to other Na-RALA versions ($.66/100 mg).  This is 3-4 times the brand we are now using.

Here is how we selected the two forms of R-lipoic acid that we are currently taking.

alpha lipoic acid best brand and form

​So given all the information, which brand delivers the biggest bang for the buck? What do you look for in an alpha lipoic acid supplement?

​There are FOUR simple steps in my opinion:

  1. Determine if the supplement contains R-Lipoic Acid
  2. ​If it does, then determine if it's a form that is known to be more bio-available such as Na-RLA or K-ALA
  3. ​Determine if any of the other ingredients have been found to cause competitive inhibition of the R-LA, like biotin or S-lipoic acid.  If so, move on to another supplement.
  4. Break the cost down by a price per 100mg.  Since daily dosing for therapeutic effects range between 300-800 mgs, you'll need to compare on a cost per day for the supplement.
  5. Once you find one you like.  Buy it.  Try it.  ​Track any markers or symptoms for changes.

The TWO we use and find to be biggest bang for the cost are:

Liquid R Lipoic Acid
Geronova Research R Lipoid Acid Liquid (K-RALA)
  • Highest bio-availability
  • R Lipoic Acid Potassium Form (K-RALA)
  • Easy liquid form
  • cost $1.20/100 mg
R LIpoic Acid LIfe Extension
​Life Extension Super R-Lipoic Acid (Na-RALA) Two-Pack, 240mg
  • High bio-availability
  • R Lipoic Acid ​Sodium Form (​Na-RALA)
  • ​Uses Geronova's Na-RALA
  • cost $​.18/100 mg

FDA Disclaimer:  The information on this website has not been evaluated by the FDA and is not intended to diagnose, treat, prevent, or cure any disease.  Please consult your physician about your health concerns.

Summary
R Lipoic Acid – The Different Forms of Lipoic Acid,  And Why You Should Care!
Article Name
R Lipoic Acid – The Different Forms of Lipoic Acid, And Why You Should Care!
Description
What is the Difference Between R-Lipoic Acid and Alpha Lipoic Acid? Which Form Should You Take? Which One Is Wasting Your Money and Could Be Harming You?
Denise
Healing Hacker
Healing Hacker
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