by Jes Williams @feelmoregooder
Alpha-lipoic acid (ALA) is a cofactor for mitochondrial alpha-ketoacid dehydrogenase complexes and is one of the most potent, natural antioxidants. (1) ALA is a sulphur-containing, multifunctional antioxidant that is endogenously produced by lipoic acid synthase in the mitochondria of many tissues, including the kidney. (3)
Alpha lipoic acid is implied often in regards to chronic inflammation, neurodegenerative ailments, and cardiovascular issues, and is also known as the “antioxidant of antioxidants.” (8) Some of the benefits of having optimal ALA levels include:
-Regulated blood sugar levels
-Enhanced insulin sensitivity
-Improved cardiovascular health
-Neutralizing free radicals in the body
-Acts as a metal chelator
-Slow progression of neurodegenerative issues (8, 10, 11)
Understanding Endogenous Compounds
This may be perhaps the most important part of this entire blog post. It has become very common for individuals to reach for a supplement for a desired, targeted outcome. With that, there’s also a general oversight for some vital questions, like: “does my body make/synthesize this compound naturally?” or “is this supplement in a form that my body can recognize and utilize?” and “what happens when I take compounds that my body is built to make?”
Compounds like melatonin, vitamin D, glutathione, etc. are actually manufactured by the body. Your body is set up to systemically create and regulate those levels, given you are putting your body in right environment to do so (primarily through light environment, circadian rhythm, and nutrients). So, what happens when you exogenously take things that your body makes? Well, according to the science and several experts in this field, negative feedback comes into play.
Negative feedback is a communication loop in which your highly intelligent physiology (which is constantly sensing your levels of a multitude of compounds in the body) that detects when exogenous intake of a substance happens. After that, the body communicates this to the brain and intrinsically downregulates your endogenous production. This is smart, and you want this to happen. Otherwise, there would be “no rules” and your body would be aimlessly producing, regardless of intake and environment.
Some are some quotations from experts & scientific papers to help you better understand this general concept of taking endogenous compounds exogenously, and how it applies to other popular supplements:
“Endogenous lipoic acid synthesis is essential for developmental survival and cannot be replaced by lipoic acid in maternal tissues and blood.” (1)
“When you take exogenous vitamin D, you're down regulating the production in your body.” - Dr. Jack Kruse (3)
“Exogenous opioids reduces endogenous opioids and that cause weight gain via the MCR system.” - Dr. Jack Kruse (4)
“Growth hormone is subject to what’s called negative feedback. If your blood levels of growth hormone are too high by virtue of injecting growth hormone, well then the pituitary can register that, the brain can register that, and then there’s a negative feedback that shuts down growth hormone.” -Dr. Andrew Huberman (5)
“Exogenous testosterone replacement therapy is a double-edged sword, posing risks to fertility due to negative feedback mechanisms on the hypothalamic-pituitary-gonadal (HPG) axis, which is the main regulator of testosterone production and spermatogenesis in males.” (6)
Endogenous Lipoic Acid Production in the Body
If you are becoming increasingly interested in ALA because of the implications in the body, we understand. We are enamored with this one, as well. A great place to start is making sure you have your foundations in place and you are targeting what your body needs to optimally create sufficient ALA.
Us humans can tend to always reach for the quick route or the magic pill - when it’s important for us to first understand this thru the lens of biology and how our bodies work. It’s imperative for us to take this step in our own learning - both for taking more accountability for our health, and also for mitigating exposure to undesirable outcomes while we desperately reach for answers & results (and meanwhile discount our biology).
For instance, your body naturally, endogenously produces opioids & feel-good neurotransmitters when exposed to unfiltered sunlight, and in response to cold exposure. (7, 9) So, instead of needing to pop pills, you can simply tap into these innate, ancient pathways in your body. Feel free to comment below if you’d like to see another cold exposure blog post to give you more insights, information, and tips.
To optimize your own body’s production of alpha lipoic acid, keep these things in mind:
-”Endogenously synthesized lipoic acid is bound to protein and functions as a cofactor for several important mitochondrial multienzyme complexes.” (12)
- the key to mitochondrial health is optimal sunlight exposure, and engaging in practices that improve mitochondrial genesis and efficiency (sauna (13), cold exposure, grounding, etc.)
-“The pathway for endogenous lipoic acid synthesis in mitochondria begins in Saccharomyces cerevisiae with the transfer of octanoic acid.” (1)
- the connection between circadian rhythm and the microbiome comes into play here, reminding us that optimizing your light environment (having brighter days and darker nights) will help endogenous ALA production
Foods Rich in ALA
The richest sources of ALA in nature are animal tissues with high metabolic activity such as the heart, liver, and kidney. for vegetable sources of ALA, the highest content is found in spinach, broccoli, tomatoes, peas, brussel sprouts, and rice. (12)
Supplementing Alpha Lipoic Acid
When looking at the pharmacological landscape of how we currently target kidney issues, ALA is a sensible option as a replacement for these drugs with a laundry list of serious side effects - that also have zero consideration for long term healthspan. (2)
Additionally, some people state that r-lipoic acid is superior advise against taking alpha lipoic acid. Alpha lipoic acid is made up of 50% r-lipoic acid and 50% s-lipoic acid. Moreover, the R and S are known as isomers or enantiomers and refer to how the molecules are shaped around the nucleus or center. Some believe that the R and S versions cancel out one another, which is not true.
Incidentally, our bodies can only use the r-lipoic acid. It actually ignores the S. However, the purified r-lipoic acid is much more expensive, which is why we would recommend using alpha lipoic acid, if you opt for a supplement.
Using Sulforaphane as a Catalyst for ALA Production
Now that we understand endogenous vs exogenous, you might wonder: “what makes sense to take?” Sulforaphane (which comes in a pure, functional, bioavailable dose in BrocElite) is not something that you endogenously create within your body.
Furthermore, the beneficial compounds in our other products are not endogenous to us, either. Thus, it makes sense to supplement them (not as a replacement to the foundations of health, but an adjunct). They act as levers for our biology and gives you the raw materials & nutrients needed to support specific pathways.
In the case of sulforaphane, studies show that amongst many other benefits, it helps boost mitochondrial biogenesis (new mitochondria), which will be supportive for more intrinsic production of ALA in your body. (14) And interestingly enough, the science backs up the other compounds that our products contain as mitochondrial-supporters:
-Resversatrol is shown to upregulate mitochondrial biogenesis factors (in a bioavailable dose in ResverElite) (15)
-Curcumin neutralizes free radicals in the mitochondria (in a bioavailable dose in CurcElite) (16)
-Quercetin can activate signaling pathways that relate to mitochondrial antioxidant defenses (in a bioavailable dose in QuercElite) (17)
-Berberine can elevate mitochondrial membrane potential (in a bioavailable dose in BerbElite) (18)
The Supplements We Choose to Make
Here at The Mara Labs we don’t just make supplements for a quick buck. If you’ve been here a while, then you know that! (and thank you, by the way for your unwavering support).
When we witness a need for a specific supplement that works, we don’t stop until we’ve made one that is rigorously tested, highly bioavailable, pure, and one we are proud of(and take ourselves). However, there are some cases where an effective form of a supplement is already out there. In this case, we tested the Vitacost brand of alpha lipoic acid. Though it does have fillers, we did find it to work and be effective in the studies we ran.
References:
- https://pmc.ncbi.nlm.nih.gov/articles/PMC1234338/
- https://www.sciencedirect.com/science/article/pii/S2590257124000336
- https://podcastnotes.org/tetragrammaton-rick-rubin/dr-jack-kruse-and-andrew-huberman-ph-d-tetragrammaton-with-rick-rubin/
- https://jackkruse.com/my-leptin-prescription/
- https://www.hubermanlab.com/episode/how-to-control-your-metabolism-by-thyroid-and-growth-hormone
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7894643/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4117380/
- https://www.mdpi.com/2076-3921/13/10/1228
- https://www.sciencedirect.com/science/article/abs/pii/0091305788902900
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9824456/
- https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/alpha-lipoic-acid
- https://lpi.oregonstate.edu/mic/dietary-factors/lipoic-acid
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7908414/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9369397
- https://pmc.ncbi.nlm.nih.gov/articles/PMC2711732/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9599178/
- https://www.sciencedirect.com/science/article/abs/pii/S0734975015300690
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7934021/
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