R-(+)-lipoic acid: feed your gut to protect your brain

Several fascinating articles have appeared recently concerning the critical importance of gut microflora¹ and the role of the gut in celiac disease and other autoimmune disorders² and how a leaky gut contributes to neurodegeneration.³ This occurs by the release of blood born toxins that adversely affect the integrity of the blood brain barrier (BBB).³

The first article by Everts¹ makes the case that we are in fact more microbe than human but that we only look human because bacterial cells are so much smaller than human cells. It also addresses the inter-individual diversity of our gut microflora and that obese people have characteristic colonies, distinct from those of lean people. The types of colonies comprising our gut flora can have a significant effect on health and disease. Everts also mentions the intentions of the human microbiome project, sponsored by NIH to more fully characterize the colonies living on and in us.⁷

The paper by Vojdani & Lambert described details of how the toxins from the gut flora lead to a break down of the tight gap junctions in both the intestines and at the BBB. This triggers an autoimmune reaction within the brain by IL-17, a cytokine secreted by Th17 cells. This causes infiltration by monocytes and macrophages (similar to the chain of events in atherosclerosis) which then induce further inflammatory reactions within the brain leading to dementia, cognitive decline, multiple sclerosis, Alzheimer’s and Parkinson’s disease.

The article by Fasano² reveals through simple but profound diagrams how wheat gluten and other antigens are recognized by the immune system which is the cause of celiac disease. He also showed how the disease is over 100 times more prevalent than previously thought. May be the most significant aspect of this article is that it provides a model for how dietary antigens can lead to other autoimmune disorders. It is well worth reading and studying because implementing these new insights could have a profound impact on your health.

Vojdani & Lambert suggested alpha lipoic acid could prevent the break down of the gap junctions in the gut and at the BBB. A recent study by a Turkish research group showed that R-Lipoic Acid protected the integrity of the BBB even from traumatic brain injury⁴.

Immediately I thought about the multiple ways RLA and R-DHLA might help prevent or mitigate these destructive & health undermining processes.

It is important to recall the history of the discovery of R-lipoic acid to show how RLA fits into this picture. Between 1937 and 1951 several groups reported an unknown “growth factor” that stimulated the growth of lactobacillis in culture medium. Lactobacillis is one of the friendly bacteria found in pro-biotics and is found in the gut. RLA was isolated in 1951 and was shown to be the essential growth factor for these microorganisms.

This suggests that although we are always trying to get higher blood levels of RLA to the heart, lungs, liver, muscles and vasculature system, we should not overlook the fact that RLA could have a significant impact on altering the patterns of microbial colonization  directly & indirectly by quenching free radicals, reducing inflammation and inducing phase II detoxification enzymes. I’ve been calling for a re-categorization of lipoic acid since I doubt that it is a direct antioxidant in vivo, the exception being in the gut, especially after a meal since free radical levels and inflammatory cytokines increase in the blood stream almost immediately after a meal.

We demonstrated that R-DHLA has a low oral (peripheral) bioavailability⁵. We saw two as yet unidentified metabolites in the blood and no significant increase in RLA when 600 mg R-DHLA was consumed. That doesn’t mean that it has no effect. We have seen and heard of many cases where a food allergy or postprandial (after a meal) reaction triggered in the gut can be rapidly quenched by RLA, R-DHLA or a combination of both. I’ve experienced this myself. Sometimes when I consume dairy or oily products I get lung congestion and/or a runny nose or sneeze attack. Consumption of any of our products usually leads to normalcy in a matter of minutes.

I’m planning a clinical trial to test this further and I’m trying to recruit experts in this area to help figure out the mechanisms. Please contact me if you have had similar experiences or are interested in participating in the trial. See also Hawrelak & Myers for an excellent review of the role of dysbiosis in health & disease⁶.

1-Everts S & C&EN Berlin. The Extended Family: Getting to Know the Trillions of Microbes Cohabitating with Humanity. Chemical & Engineering News (July 20, 2009) 87(29) 43-46.

2-Fasano A. Surprises from Celiac Disease. Sci Am (2009) 301(2) 54-61.

3-Vojdani A, Lambert J. The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part II. Evid Based Complement Alternat Med (2009)  

4- Toklu HZ, Hakan T, Biber N, Solakoglu S, Ogunc AV, Sener G. The protective effect of R-alpha lipoic acid against traumatic brain injury in rats. Free radical research (2009) 43(7) 658-667.
The original title only referred to LLA but they in fact used R-lipoic acid. The addition of “R-“ is mine.

5- Carlson DA, Young KL, Fischer SJ, Ulrich H. An evaluation of the stability and plasma pharmacokinetics of R-lipoic acid (RLA) and R-dihydrolipoic acid (R-DHLA) dosage forms in human plasma from healthy volunteers. Chapter 10 in Alpha Lipoic Acid: Energy Production, Antioxidant Activity and Health Effects. Packer L, Patel M, eds. Boca Raton, New York, London: Taylor & Francis Publishers (2008) 235-270.

6- Hawrelak JA & Myers SP. The Causes of Intestinal Dysbiosis: A (Review) Alt Med Rev. (2004) Volume 9 (2) 180-197.
http://www.thorne.com/altmedrev/.fulltext/9/2/180.pdf

7- http://nihroadmap.nih.gov/hmp/