Ben Franklin said it best when he said “an ounce of prevention is worth a pound of cure”. This is especially true of Alzheimer’s Disease (AD). There is overwhelming evidence that the neurofibrillary tangles and beta-amyloid plaques (AB) seen in AD are not a cause, but an effect of the disease process. Similarly, there is evidence that AB deposits themselves are not a signature of neurotoxicity, per se, but of oxidative imbalance and an oxidative stress response in the brain (1).

The reason we haven’t been able to find a cause for AD is because there is no cause… Or rather, there is no one cause. AD is a multifactorial disease, each case having it’s own causative factors and unique set of symptoms and story. The real kicker is that inflammatory diseases like AD actually cause changes in gene expression and protein function and further perpetuate the inflammatory state. In other words, the inflammation seen in AD can be induced by numerous things by our environment and then maintaned by the body without any further insult, creating a vicious cycle.

So, my friends, the time to act is now. Not tomorrow. Not next week. Right now.
I have already written about ways to reduce your inflammatory burden (ex: losing weight). Let’s talk about what we can do to try to shut off the vicious cycle and get rid of the inflammation we already have.. Of course, all of these supplements would be great for someone who already has AD, but they will be the most effective and protective in people who are not yet afflicted with the full-blown disease.

Inflammation is mediated by many receptors, proteins and enzymes. One example of such a receptor is RAGE, the receptor for advanced glycation end-products. The most well known AGE today is HbA1C, the marker for glycosylated hemoglobin used to track blood sugar in diabetic patients. HbA1C is a marker of inflammatory stress and high AGEs, and therefore the higher your HbA1C, the more critical it is that you get that blood sugar under control. RAGE has been implicated to play an important role in AD.

Interestingly, all of these pathways eventually feed back into one major loop that is mediated by the Nuclear Factor Kappa Beta (NF-KB). For example, RAGE triggering leads to activation of NF-KB and it’s pro-inflammatory signals, which in turn stimulates RAGE and leads to a vicious cycle of inflammation (2). The major inhibitor of NF-KB is NRF-2, known as the keeper of redox homeostasis. Therefore, effective methods to get the core of inflammation would and should include foods and supplements that 1. stimulate NRF2 2. Inhibit NF-KB and 3. Boost antioxidants such as glutathione.

Curcumin, a component of the yellow curry spice tumeric, is a hot topic these days- and it’s no wonder why. Not only is curcumin a NF-KB inhibitor, but it has several neuroprotective effects that make it uniquely suited for the prevention of AD. Among it’s many antioxidant and protective effects, curcumin has been shown to bind AB and increase it’s uptake by white blood cells (3), making it an enticing treatment for AD. Curcumin has been shown to be a potent free radical scavenger- more so than vitamin E. Curcumin has been shown to chelate metals such as Iron and Copper, excess of both of which have been implicated in the pathogenesis of AD (4). Unfortunately, curcumin has relatively low bioavailability on it’s own. There are quality products available today that are readily absorbed (I personally like the one from Apex Energetics), but these products need to be ordered by a physician. Many functional medicine doctors are familiar with this company and can help you determine if this product is for you (it is). : )

Resvertrol, a flavanoid in red wine, has been shown to have many effects similar to curcumin. Resvertrol is a potent inhibitor of the NF-KB pathway, and it has been shown to increase the clearance of AB (4). It also protects DNA, decreases cell death, and decreases inflammation. Resvertrol is also not very bioavailable on it’s own, but like curcumin, there are products available today that are better absorbed by the body.

Omega-3 fatty acids (fish oils) are another hot topic in nutrition these days. Generally, omega-3s are known to decrease inflammation, but one particular omega-3, DHA, has been shown to be especially neuroprotective. DHA has been shown to stimulate transthyretin, a protein possibly involved in the clearance of AB (4).

EGCG, the major component of green tea flavanoids, is another great source of antioxidants that may show particular benefit in AD. EGCG has been shown to chelate iron and copper, function as an antioxidant, and elevate and up-regulate enzymes that produce other antioxidants such as superoxide dimutase and catalase (4). Green tea is a great, easy way to get antioxidants into your daily routine. To get the most out of your green tea (and make it taste WAY better), check out this website for green tea brewing tips: http://www.thefragrantleaf.com/brewingtips.html

Glutathione is the body’s most important antioxidant- particularly in the brain. Glutathione is also critically important in detoxification in the liver, so anyone who has or is taking a lot of drugs (medications or illegal) or alcohol should consider boosting their stores. While the body does make it’s own glutathione, taking precursors such as N-Acetyl Cysteine can help give you a boost in times of stress. Quite frankly, in the world we live in now I think we are literally surrounded by stressors and should be taking some of this every day. Naturopathic doctors (NDs) may offer IV glutathione in their practices, which is a great way to get a boost of this important antioxidant (as long as you’re not afraid of needles, that is)..

There are many, many supplements that are being studied for their benefits in AD… Honestly, this is just the tip of the iceberg! Of course, I know nobody wants to take a zillion pills a day, weather they be medications or supplements, so this list is the ones I deem the most important and effective at this time.

May your oxidants be neutralized, followers!

Nikki

Resources:
(1) Siddharatha Mondragon-Rodrigues et al “Causes versus effects: the increasing complexities of Alzheimer’s disease pathogenesis” Expert Rev Neurother 2010 May; 10(5): 683-691 (PMID: 20420489)
(2) Lorena Perrone “The complexity of sporadic Alzheimer’s Disease pathogenesis: the role of RAGE as a therapeutic target to promote neuroprotection by inhibiting neurovascular dysfunction” Int J of Alzheimer’s D March 11, 2011 (PMID: 22482078)
(3) Dumont Magali “Mitochondria and antioxidant targeted therapeutic strategies for Alzheimer’s Disease” J Alz Dis 2010; 20(2) (PMID: 20421689)
(4) Ramesh Balenahalli et al “Neuronutrition and Alzheimer’s Disease” J Alz Dis Jan 2010; 19(4): 1123-1139 (PMID: 20308778)

Special note: I have started including citations with a PubMed ID number, PMID. Now all you have to do to read my references (or at least the abstracts), is go to pubmed.gov and type the PMID number in the search field!