Lipoic Acid and Combined Supplements for Alzheimer's Disease

Promising findings for non-pharmacologic treatments.

Posted Mar 14, 2019

This is the fourth in a series on complementary and alternative and integrative treatments of dementia. Previous posts reviewed the evidence for dietary changes, multi-modal interventions and a promising natural product called Huperzine derived from Chinese herbal medicine. This post is offered as a concise review of lipoic acid (also called alpha lipoic acid) a naturally occurring molecule in humans and many animals that plays essential roles in metabolism. Lipoic acid is found in red meat, broccoli, tomatoes, spinach, and Brussels sprouts. It is used for weight loss and is widely prescribed in some European countries to treat diabetes, including a painful complication called diabetic neuropathy. LA is generally safe even when taken at high doses (2 to 3 grams per day) and may cause mild nausea, itching or rash. Absorption is best when taken on an empty stomach, 30 to 60 minutes before eating or a few hours after eating. 

Promising but preliminary findings but few human studies

Findings from animal studies suggest that lipoic acid may slow the rate of cognitive deterioration in the early stages of Alzheimer’s disease. Beneficial effects are mediated by several mechanisms including increasing synthesis of acetylcholine, an important neurotransmitter required for the formation of new memories; increasing the activity of enzymes needed to synthesize glutathione, an important antioxidant; and savaging free radicals thus reducing inflammation in the brain that may increase the risk of developing Alzheimer’s disease (Maczurek et al 2008).  

Few human clinical trials have been done on lipoic acid (LA) in individuals diagnosed with Alzheimer’s disease but most published findings are positive. In a small open pilot study, 9 patients with probable AD were treated with lipoic acid 600mg daily for one year while taking cholinesterase inhibitors. All patients experienced stabilization in cognitive functioning which had previously been declining at a steady rate (Hager et al 2001). That open study was extended to 48 months and enlarged to include 43 patients diagnosed with mild Alzheimer’s disease, all of whom experienced a significant slowing in the rate of cognitive deterioration during the study period (Hager et al 2007). Although promising, the significance of the above findings is limited by the absence of a placebo control arm and small study size, hence they should be regarded as preliminary pending confirmation by a large double-blind placebo-controlled trial.

Combining lipoic acid with other natural substances may be more effective than any single nutraceutical 

In addition to research on lipoic acid only, studies have investigated nutraceutical formulas that include LA in combination with other natural products known to have beneficial antioxidant or neuroprotective properties. An epidemiologic study found that individuals who regularly consume fruits and vegetables rich in polyphenols have a significantly reduced risk of developing Alzheimer’s disease (Dai et al 2006). Polyphenols are often recommended by health care providers because of their established protective effects against cancer and cardiovascular disease. Along similar lines, elderly individuals who frequently consume curry (which contains the antioxidant curcumin) or foods rich in the omega-3 fatty acid DHA, may have a significantly decreased risk of Alzheimer’s disease (Ng et al 2006; Morris et al 2003; Tully et al 2003). Curcumin is a more potent free radical scavenger than vitamin E and may inhibit the build-up of amyloid beta plaque, one of the main causes of Alzheimer’s disease (Zhao 1989; Yang et al 2005). Mice that were genetically modified (i.e., transgenic mice) to develop Alzheimer’s disease were found to have significantly reduced amyloid levels after 6 months on a high curcumin diet (Yang et al 2005). Epigallocatechin gallate (EGCG), a molecule that occurs naturally in green tea, is another nutraceutical that has attracted recent attention because it prevents neuronal cell death caused by amyloid beta neurotoxicity in cell cultures and transgenic mice (Choi et al 2001; Rezai-Zadeh 2005). Findings of recent animal studies suggest that the omega-3 fatty acid DHA may help prevent AD by reducing amyloid beta accumulation thus decreasing the neurotoxic effects of amyloid beta (Florent 2006; Hashimoto 2005).

Human studies on combination treatments are needed

As the above nutraceuticals prevent or delay the progression of Alzheimer’s disease via different mechanisms, combining them into a single formula might be more effective than any nutraceutical alone. In fact, findings of a recent animal study bear this out. In a just-published study, transgenic mice predisposed to develop Alzheimer’s disease treated with a combination of lipoic acid, curcumin, and the omega-3 fatty acid DHA were found to have greater anti-inflammatory and neuroprotective effects compared to mice receiving only one nutraceutical (Sharman et al 2019). A large placebo-controlled trial in humans diagnosed with Alzheimer’s disease is needed to determine whether combining multiple nutraceuticals is more effective than single nutraceuticals. This is the domain of so-called multi-modal interventions, which I discussed in a previous post.

You can read more about complementary and alternative treatments of Alzheimer’s disease and mild cognitive impairment in my book “Dementia and Mild Cognitive Impairment: The Integrative Mental Health Solution.”