To say type 2 diabetes (T2D) and related comorbidities stemming from chronic hyperglycemia and hyperinsulinemia are epidemic is an understatement. In the industrialized world of the 21st Century people who have healthy glucoregulation and insulin signaling are the exception not the norm. A low-carb diet is one of the most powerful and effective non-pharmaceutical and non-surgical interventions for lowering blood sugar and insulin and for decreasing inflammation and oxidative stress.

That being said sometimes even when individuals change their diet and lifestyle habits they still need some extra help. Chromium magnesium and inositol spring immediately to mind for being useful here. Beyond that there are other nutrients that are especially beneficial for improving the downstream complications of T2D. To find one all we have to do is go right to the beginning of the alphabet: alpha-lipoic acid. 

Alpha-lipoic acid (ALA not to be confused with the omega-3 fat alpha-linolenic acid) is a sulfur-containing compound that exhibits amphiphilic antioxidant properties. (It works in both aqueous and lipid environments—cytosol plasma membranes serum and lipoproteins.) Lipoic acid is best known for its antioxidant capacity but this molecule has also been shown to have potent effects on blood glucose control via improved insulin secretion and sensitivity. (This diagram offers a nice summary of ALA’s multiple influences.)

Humans synthesize small amounts of ALA so it’s not an essential nutrient although it was once classified as a vitamin before it was known that humans do produce some endogenously. (The precursor is octanoic acid or C:8 caprylic acid.) However even though we do generate ALA as is true for so many nutrients certain patient populations may benefit from higher amounts than they produce and amounts higher than they would typically get from food. The richest dietary sources of ALA are mammalian proteins with high metabolic activity such as heart liver and kidney—not exactly regular features on dinner tables in North America. Plant foods also contain ALA but in much smaller amounts. In order to get pharmacological benefits from ALA a pharmacological dose would be more appropriate.

Higher doses—orders of magnitude greater than that which is endogenously produced or available in food—have been shown to be safe in animal studies. The no-observed-adverse-effect level is considered to be 60 mg/kg of bodyweight per day and studies using oral ALA for diabetic neuropathy at doses as high as 1800 mg/day for six months and 1200 mg/day for two years did not result in serious adverse effects.

Regarding diabetes studies demonstrate that lipoic acid aids in glucoregulation by facilitating proper functioning of the insulin receptor and recruitment of insulin-sensitive and insulin-independent glucose transporters (GLUT-4 and GLUT-1 respectively) to muscle and adipose cell membranes. These seem to be the main mechanisms by which ALA increases glucose disposal. Its effects on glucose transporters led researchers to say that ALA has “insulin mimetic” activity. And considering that many type 2 diabetics are actually already hyperinsulinemic it might be helpful to have a compound that has a glucose-lowering activity without adding more insulin to the fire. 

The benefits of ALA for diabetic complications are so well-regarded that ALA is available as a prescription “drug” for neuropathy in Germany. Reviews and meta-analyses support the impressive efficacy of ALA for neuropathy. Beyond neuropathy diabetics often have compromised energy generation resulting in fatigue. ALA is “an essential cofactor for several mitochondrial enzyme complexes that catalyze critical reactions related to energy production and the catabolism (breakdown) of α-keto acids and amino acids.”  Another common comorbidity of T2D is compromised vascular function. A double-blind randomized placebo-controlled trial showed that compared to placebo 600 mg/day of intravenous ALA for 21 days improved endothelium-dependent vasodilatation in T2 diabetics. ALA has also been shown to improve nitric oxide-mediated vasodilation in diabetic patients.

Researchers looking at ALA for vascular function have hypothesized that ALA helps by reducing oxidative stress “particularly in patients with imbalance between increased oxidative stress and depleted antioxidant defense.” This is a plausible mechanism. ALA is also called thiocitic acid which advertises its sulfur content. It has been called an “antioxidant of antioxidants.” In its reduced form (dihydrolipoic acid DHLA) it serves to recycle vitamins E and C coenzyme Q₁₀ and glutathione. Coupled together oxidized and reduced lipoic acid have a greater redox potential than oxidized and reduced glutathione leading some researchers to refer to lipoic acid as a “universal antioxidant.” This being the case it’s hard to imagine a tissue system ALA wouldn’t have a beneficial impact on. 

Owing to its potential insulin-mediated glucose-lowering effects patients adding ALA to a regimen that includes insulin should be monitored closely to ensure healthy blood glucose levels.