March 2013 From: Dale Bredesen, MD, Professor, Buck Institute

Following up with a number of friends and colleagues about our research on Alzheimer’s disease and its relation to the physiological processes underlying memory formation and forgetting, I am putting together a list of suggestions for you to discuss with your neurologist, internist, or family physician. Here is the rationale and data related to these:

1. 1) Check your homocysteine and vitamin B12. This is a simple blood test, and the higher the homocysteine, the greater risk for Alzheimer’s disease (AD). Furthermore, higher homocysteine is associated with more rapid atrophy (shrinkage) of the hippocampus, a key brain area for memory (and one that is a central site for AD). 
   In the past it was thought that risk occurred when homocysteine exceeded 13 (13 micromolar), but it is now recommended that we keep our homocysteine levels at 6 or below. It is easy to do this by taking vitamin B6 (10mg; some prefer to take this as pyridoxal-5-phosphate rather than pyridoxine), B12 (1mg; best to take this as methylcobalamin or hydroxocobalamin instead of the usual cyanocobalamin), and folate (0.8mg; some prefer to take this as methyl-tetrahydrofolate instead of folate). If these simple vitamins do not succeed in reducing homocysteine to 6, then you can add trimethylglycine (also called betaine), 250mg or 500mg per day.
    

2. 2) A mountain of data support an important role for inflammation in Alzheimer’s disease (AD) (as well as in aging), with multiple mechanisms involved. It is easy to check your own body’s status of inflammation: you can check your CRP (C-reactive protein; this is a high-sensitivity test sometimes referred to as hs-CRP for “high sensitivity CRP”), and also your A/G ratio (albumin to globulin ratio). These are both routine blood tests. Your CRP should be 1 or lower, and your A/G ratio should be 1.5 or higher (best when 1.8 or higher).

   There are several keys to lowering inflammation:
    

   1. (1) minimize eating saturated fats;

   2. (2) minimize simple carbohydrates (sugar, bread, etc.);

   3. (3) take omega-3-rich oils (e.g., fish oil) or foods rich in alpha-linolenic acid—like flaxseed, walnuts, and canola oil;

   4. (4) exercise;

   5. (5) keep waist size less than 35 inches (for women) or 40 inches (for men);

   6. (6) reduce stress;

   7. (7) get at least 7 hours of sleep each night (preferably 8);

   8. (8) optimize hygiene (with regular baths or showers, cleaning under nails, regular tooth brushing; some like to clean sinuses, as well, whereas others prefer not to include this);

   9. (9) some like to take anti-inflammatory herbs, such as Ashwagandha (Withania somnifera), 500mg-1000mg, or spices, such as ginger (one or two 500mg capsules) or turmeric (400-600mg);

   10. (10) make sure not to smoke;

   11. (11) make sure you do not have a sensitivity to wheat (or the gluten from wheat), because, if you do, then this can underlie chronic inflammation. You can check this by getting food allergy testing, and, if you are sensitive, you can cut out the wheat.
        

3. 3) Check your vitamin D. Although vitamin D might sound like a typical vitamin, it is anything but:

   	first of all, vitamins are typically not made by your body, which is why you need to have these in your diet, but you do actually make vitamin D—sunlight converts a cholesterol molecule called 7-dehydrocholesterol into pre-vitamin D, but at that point, the story is far from over, since the newly synthesized vitamin D is inactive. Next, your liver, and then your kidneys (and certain cells in your immune system), convert the vitamin D to active vitamin D, which is 1,25 dihydroxycholecalciferol (also called calcitriol). So your body can indeed make vitamin D, but typically it is not enough for good health, so it is a good idea to obtain some vitamin D in our diets.
   	Second, vitamin D, unlike other vitamins, is actually a steroid (truly a performance-enhancing steroid, since it keeps your body healthy in a number of ways). Once activated by your liver and kidneys, it circulates in your body as a hormone, much like thyroid hormone, and binds to its own receptor—vitamin D receptor—which then binds to your DNA and turns on over 100 genes, all over your body, leading to myriad effects. Vitamin D affects bone metabolism, helps to suppress cancer formation, reduces inflammation, appears to inhibit the development of Alzheimer’s disease, affects cardiovascular disease, and has many other effects.
   		With all of the many effects of vitamin D, it is perhaps not surprising that the optimal intake and serum level of vitamin D are matters of controversy: it used to be said that a serum level of 25-hydroxycholecalciferol (this is the most commonly measured form, and is the inactive form that is activated by the kidneys) of 20-30ng/ml is fine, but many now believe that optimal levels are 50-80, not 20-30. In any case, since low levels are associated with numerous problems, from cardiovascular disease to cancer to Alzheimer’s disease, it is helpful to know your own level. Then you can use a rule of thumb—the 100x rule—to figure out your optimal dose of vitamin D (typically taken as vitamin D3): decide on your goal, subtract your current value, and multiply by 100 to get the dose. For example, if your goal is 50, and you find out that your current level is 25, then you could take 2500IU per day. Toxicity has not been shown for any intakes less than 10,000IU per day, so it is a safe vitamin.

    

4. 4) Check your hemoglobin A1c. This gives you an indication of your average glucose over the past 1-2 months, so it is better than a spot check of your glucose. It should be 5.5 or less. Anything over 6.0 is pre-diabetic, and anything over 7.0 indicates diabetes. Higher hemoglobin A1c is also associated with more atrophy (shrinkage) of the hippocampus, which is a critical area of the brain for memory, and an area damaged early and severely in Alzheimer’s disease.
    

5. 5) Check your hormone status, including thyroid (free T3, free T4, reverse T3, and TSH), pregnenolone, testosterone, estrogen, and progesterone. Be careful—the generally accepted “normal” levels for these are too inclusive, so that, if you are toward the bottom of the “normal” level, you may want to discuss this with your physician. Hormone levels can be normalized, and this also helps maintain optimal cognitive function.

For more information, please contact
Kris Rebillot
Director of Communications
krebillot@buckinstitute.org
www.thebuck.org