Natural Supplements to Ward Off Alzheimer’s (Aging on the Brain: The Neurodegenerative Battle)

Alzheimer’s disease is a neurodegenerative disease that destroys brain cells, resulting in memory loss and problems with thinking, behavior, lifelong hobbies and social life. It is a progressive and fatal disease without a current cure. It affects both men and women usually 65 years and older, but an early-onset form also exists. Before his death on April 5, 2008, Charlton Heston publicly announced in 2002 he was suffering from symptoms synonymous with Alzheimer’s disease. Alzheimer’s is the seventh leading cause of death in the United States; as many as 5 million Americans are living with the disease, according to the National Alzheimer’s Association (Alz.org)

One of the characteristics of Alzheimer's disease is the deposition of senile plaques containing amyloid-beta (A beta), a protein that promotes inflammation and oxidation. Natural supplementation is becoming a popular preventive method for Alzheimer's disease and other neurodegenerative diseases, by enhancing memory and cognitive functions.

Curcumin, the principal curcuminoid in the Indian curry spice turmeric, for example, has shown antioxidant and anti-inflammatory qualities. A study at the University of California Los Angeles (UCLA) School of Medicine treated macrophages, cells within the tissues that originate from specific white blood cells, from six Alzheimer’s patients and three controls with curcuminoids (as Curcumin C3 Complex, from Sabinsa) in vitro, and measured A beta uptake.¹ After treating the macrophages with curcuminoids, A beta uptake by macrophages of three of the six Alzheimer’s patients was significantly increased (P<.001 to .081).

In 2008, an in vitro model of alpha-synuclein (AS) aggregation, was developed by treatment of purified AS protein with Fenton reaction.² Alpha-synuclein is the primary structural component of Lewy bodies, which are abnormal aggregates of protein (alpha-synuclein) that develop inside nerve cells; an alpha-synuclein fragment, known as the non-A beta component (NAC), is found in amyloid plaques in Alzheimer’s. The addition of curcumin inhibited aggregation in a dose-dependent manner and increased AS solubility. Next, the aggregation-inhibiting effect of curcumin was investigated in a cell culture utilizing catecholaminergic SH-SY5Y cell line. A model system was developed in which the red fluorescent protein (DsRed2) was fused with A53T mutant of AS and its aggregation examined under different concentrations of curcumin. More than a 32 percent decrease in mutant AS aggregation was observed within 48 hours after the curcumin was added.

A Korean study synthesized eight novel derivatives of curcumin and dehydrozingerone, and their binding affinities for A beta aggregates were measured.³ Fluoropropyl-substituted curcumin showed the highest binding affinity (Ki=0.07 nM).

Another study published in the Journal of Neurochemistry used in vivo multiphoton microscopy (MPM) to demonstrate that curcumin crosses the blood-brain barrier and labels senile plaques and cerebrovascular amyloid angiopathy (CAA) in amyloid precursor protein (APP) mice.⁴ Systematic treatment of mice with curcumin cleared and reduced existing plaques after seven days, suggesting a potent disaggregation effect. Curcumin also led to a limited, but significant, reversal of structural changes in dystrophic dendrites, including abnormal curvature and dystrophy size.

At UCLA, under aggregating conditions in vitro, curcumin inhibited aggregation as well as disaggregated fibrillar A beta40.⁵ Curcumin was a better A beta40 aggregation-inhibitor than ibuprofen and naproxen, and it prevented A beta42 oligomer formation and toxicity and decreased dose dependently A beta fibril formation.

Omega-3 essential fatty acids (EFAs) are known to improve cognitive function as well. At Karolinska University Hospital Huddinge, Stockholm, a randomized, double blind, placebo-controlled, clinical trial administered 1.7 g/d of docosahexaenoic acid (DHA) and 0.6 g/d of eicosapentaenoic acid (EPA) or a placebo to 204 patients with Alzheimer’s disease for six months, after which all 204 patients received omega-3 fatty acid supplementation for six more months.⁶ A total of 174 patients completed the trial. At six months, the decline in cognitive function did not differ between the groups; however, in a subgroup (n=32) with very mild cognitive dysfunction, a significant (P<.05) reduction in Mini-Mental State Examination (MMSE) decline rate was observed in the omega-3 EFA-treated group compared with the placebo group. A decline rate was seen between six and 12 months in this placebo subgroup when receiving omega-3 supplementation.

A separate study at UCLA took aged animals (17 to 19 months old) and placed them in one of three groups until they were 22.5 months of age: control (0.09 percent DHA), low DHA (0 percent) or high DHA (0.6 percent) chow.⁷ The DHA-enriched diets significantly reduced the total A beta by more than 70 percent when compared to the low DHA and control chow diets. Dietary DHA also decreased A beta42 levels below those seen with the control chow. The overall plaque burden was significantly reduced by 40.3 percent.

In a study published in The Journal of Neuroscience, researchers reported DHA significantly increases LR11, a neuronal sorting protein that reduces APP trafficking to secretases that generate A beta, in primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw Alzheimer’s mouse model.⁸ DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also seen with dietary fish oil in young rats with insulin resistance. Because reduced LR11 is known to increase A beta production and may be a significant genetic cause of late-onset Alzheimer’s disease (LOAD), the results indicated DHA increases LR11 levels and may play an important role in preventing LOAD.

A study at Radboud University Nijmegen, Netherlands, administered regular rodent chow, a Typical Western Diet (TWD) containing 1 percent cholesterol, or a diet with a high (0.5 percent) level of DHA to mice starting at six months of age, for 12 months.⁹ The TWD diet increased plaque burden in the dentate gyrus of the hippocampus, but did not significantly reduce relative cerebral blood volume (rCBV). The DHA-enriched diet increased rCBV, without changing blood flow and decreased the amount of vascular beta-amyloid deposition.

Conversely, a 2007 study gave APP double-transgenic mice, as well as nontransgenic (NT) normal littermates, from two to nine months of age, a high omega-3 supplemented diet or a standard diet with a comprehensive behavioral test battery administered during the final six weeks.¹⁰ The results suggested diets high in omega-3 fatty acids, or use of fish oil supplements (DHA+EPA), will not protect against Alzheimer's disease, at least in high-risk individuals. However, normal individuals conceivably could derive cognitive benefits from high omega-3 intake if it corrects an elevation in the brain level of omega-6 fatty acids as a result. Alternatively, dietary fish may contain nutrients, other than DHA and EPA, which could provide protection against Alzheimer's disease.