Advanced Mediterranean Diet

Neurology a few days ago reported that the proper diet seems to help prevent age-related brain shrinkage and cognitive decline.

From the press release:

People with diets high in several vitamins or in omega 3 fatty acids are less likely to have the brain shrinkage associated with Alzheimer’s disease than people whose diets are not high in those nutrients, according to a new study published in the December 28, 2011, online issue of Neurology, the medical journal of the American Academy of Neurology.

Those with diets high in omega 3 fatty acids and in vitamins C, D, E and the B vitamins also had higher scores on mental thinking tests than people with diets low in those nutrients. These omega 3 fatty acids and vitamin D are primarily found in fish. The B vitamins and antioxidants C and E are primarily found in fruits and vegetables.

So the dietary pattern linked to preservation of brain size and function in this study is: high omega-3 fatty acids and vitamins B, C, D, and E.  I don’t know if study participants were getting these nutrients from supplements or from food or a combination.  (I haven’t read the full article.)

Don’t forget: our bodies can make vitamin D if we have enough sun exposure.  So supplements and food would not be the only sources.

Note that the time-honored Mediterranean diet is also associated with lower rates of dementia and slower rate of age-related mental decline.

I previously reported that a supplement cocktail of three B vitamins slowed the rate of brain shrinkage.  Have those researchers reported yet whether the supplements helped preserve brain function?

Steve Parker, M.D.

Reference: Bowman, G.L., et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging.  Neurology.  doi: 10.1212/WNL.0b013e3182436598

h/t to Randall Parker at FuturePundit

Insulin administered via the nasal passages slowed or stabilized mental functioning and functional abilities in a pilot study of people with Alzheimer disease and mild cognitive impairment, according to Seattle-based investigators.

As you probably know, dementia is a huge problem for our aging population, and Alzheimers is the most common form of dementia.  The Mediterranean diet is associated with lower risk of mild cognitive impairment and has long been linked to lower risk of dementia as well as slower mental decline in existing Alzheimer dementia patients.  The Mediterranean diet also seems to prolong life in Alzheimer patients.  So I’m always interested in ways to prevent and treat Alzheimers.  Mild cognitive impairment is often a precursor to Alzhiemer disease.

Methodology

The study involved 104 non-diabetic participants with Alzheimer disease (40) or amnestic mild cognitive impairment (64).  They were randomly assigned to one of three groups: placebo (control group), nasal insulin 20 IU twice daily, or nasal insulin 40 IU twice daily. 

Insulin was delivered through a ViaNase device which releases the insulin in to a chamber covering the nose; the participant breathes regularly for two minutes to pick up the dose.  This insulin goes directly to the central nervous system without affecting blood insulin levels or blood sugar levels.

Mental and functional abilities (for example, activities of daily living) were measured at baseline, then again 2, 4, and 6 months later.  Some of the participants (23) underwent lumbar puncture (for dementia biomarker analysis) and PET brain scans (18).

Comments

This was a well-designed pilot study.

Nasal insulin was well-tolerated.  It’s not commercially available in the U.S.

Regarding the placebo group, I was surprised that the researchers could document mental and functional deterioration over this relatively short-term study (4–6 months).  I’m impressed with the need to treat age-related cognitive decline early and aggressively, when we have something that works.

How would nasal insulin work?  We don’t know for sure, but it seems to relate to insulin’s effect on

• the ability of neurons (brain cells) to communicate with each other through synapses
• modulaton of blood sugar metabolism in the hippocampus and other brain areas
• facilitation of memory
• ß-amyloid peptide

In case you’re wondering, standard subcutaneous injections of insulin can’t be used in studies like this because of the risk of low blood sugar.

I agree wholeheartedly with study authors that “these promising results provide an impetus for longer-term trials of intranasal insulin therapy in adults with amnestic mild cognitive impairment or Alzheimers disease.”

Psychiatrist Emily Deans blogged about this study at Evolutionary Psychiatry September 21, 2001.  Please see her cogent remarks.

Steve Parker, M.D.

Reference:  Craft, Suzanne, et al.  Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment.  Archives of Neurology, 2011.  doi: 10.1001/archneurol.2011.233

The Mediterranean diet slowed age-related mental decline in elderly Chicago residents, according to researchers at Rush University Medical Center.  The investigators noted that a Manhattan population following the Mediterranean diet also showed slower mental decline and lower rates of Alzheimers dementia.Over 3,000 study participants (2,280 blacks, 1,510 whites) were studied for an average of eight years.  Food consumption was determined by questionnaires, and mental function was tested every three years.  Adherence to the Mediterranean diet was judged according to a Mediterranean diet score developed by Panagiotakis, et al.

The greater the adherence to the Greek-style Mediterranean diet, the lower the rate of mental decline over the course of the study.

Mental decline to some extent is a normal part of aging.  If we can avoid it or lessen it’s impact, why not?  A couple ways to do that are regular exercise and the Mediterranean diet.

Would a low-carb Mediterranean diet work just as well or better?  Nobody knows yet.

Steve Parker, M.D.

Reference:  Tangney, Christine, et al. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population.  American Journal of Clinical Nutrition, 2010.  doi 10.3945/ajcn.110.007369

I’ve found that nearly everbody’s eyes glaze over if I try to explain how, physiologically, the Mediterranean diet promotes health and longevity.  Below are some of the boring details, for posterity’s sake, from my 2007 book, The Advanced Mediterranean Diet: Lose Weight, Feel Better, Live Longer.

Many of the nutrient-disease associations I mention below are just that: associations, linkages, not hard proof of a benefit.  Available studies are often contradictory.  For instance, there may be 10 observational studies linking whole grain consumption with reduced deaths from heart disease, while three other studies find no association, or even suggest  higher death rates. (I’m making these numbers up.)  If you want hard proof, you’ll have to wait.  A long time.  Such is nutrition science.  Take it all with a grain of salt. 

Also note that the studies supporting my claims below are nearly all done in non-diabetic populations.

Coronary Heart Disease

Coronary heart disease, also known as coronary artery disease, is the No.1 cause of death in the world. It’s responsible for 40% of deaths in the United States and other industrialized Western countries. The Mediterranean diet is particularly suited to mitigating the ravages of coronary heart disease. Mediterranean diet cardiac benefits may be related to its high content of monounsaturated fat (in olive oil), folate, and antioxidants.

The predominant source of fat in the traditional Mediterranean diet is olive oil, which is rich in monounsaturated fatty acids. High intake of olive oil reduces blood levels of triglycerides, total cholesterol, and LDL (”bad”) cholesterol. HDL or “good” cho-lesterol is unaffected. Olive oil tends to lower blood pressure in hypertensive people. Monounsaturated fatty acids reduce cardiovascular risk substantially, particularly when they replace simple sugars and easily digestible starches. Monounsaturated fatty acids and olive oil may also reduce breast cancer risk. The cardioprotective (good for the heart) and cancer-reducing effects of olive oil may be partially explained by the oil’s polyphenolic compounds.
    
Nuts are another good source of monounsaturated fatty acids and polyunsaturated fatty acids, including some omega-3 polyunsaturated fatty acids. Nuts have been proven to be cardioprotective. They lower LDL and total cholesterol levels, while providing substantial fiber and numerous micronutrients, such as vitamin E, potassium, magnesium, and folic acid. Compared with those who never or rarely eat nuts, people who eat nuts five or more times per week have 30 to 50% less risk of a fatal heart attack. Lesser amounts of nuts are also cardioprotective, perhaps by reducing lethal heart rhythm dis-turbances. 
    
Another key component of the Mediterranean diet is fish. Fish are excellent sources of protein and are low in cholesterol. Fatty, cold-water fish are particularly good for us because of their omega-3 polyunsaturated fatty acids: eicosapentaenoic acid (EPA) and docosahexanaenoic acid (DHA). The other important omega-3 polyunsaturated fatty acid is alpha-linolenic acid (ALA), available in certain plants. Our bodies can convert ALA into EPA and DHA, but not very efficiently. Fish oil supplements, which are rich in EPA, lead to lower total cholesterol and triglyce-ride levels. Fish oil supplements have several properties that fight atherosclerosis (hardening of the arteries). In people who have already had a heart attack, the omega-3 polyunsaturated fatty acids have proven to dramatically reduce cardiac deaths, especially sudden death, and nonfatal heart attacks. So omega-3 polyunsaturated fatty acids are “cardioprotective.”

The first sign of underlying coronary heart disease in many people is simply sudden death from a heart attack (myocardial infarction) or heart rhythm disturbance. These unfortunate souls had hearts that were ticking time bombs. I have little doubt that a significant number of such deaths can be prevented by adequate intake of cold-water fatty fish. As a substitute for fish, fish oil supplements might be just at beneficial. The American Heart Association also recommends fish twice weekly for the general population, or fish oil supplements if whole fish isn’t feasible. Compared with fish oil capsules, whole fish are loaded with vitamins, minerals, and protein. The richest fish sources of omega-3 polyunsaturated fatty acids are albacore (white) tuna, salmon, sar-dines, trout, sea bass, sword-fish, herring, mackerel, anchovy, halibut, and pompano.
    
Cardioprotective omega-3 polyunsaturated fatty acids (mainly ALA) are also provided by plants, such as nuts and seeds, legumes, and vegetables. Rich sources of ALA include walnuts, butternuts, soy-beans, flaxseed, almonds, leeks, purslane, pinto beans, and wheat germ. Purslane is also one of the few plant sources of EPA. Several oils are also very high in ALA: flaxseed, canola, and soybean. Look for them in salad dressings, or try cooking with them.

Macular Degeneration

Omega-3 fatty acid and fish consumption may also be “eye-protective.” Eating fish one to three times per week apparently helps prevent age-related macular degeneration (AMD), the leading cause of blindness in people over 50 in the United States. While AMD has a significant hereditary component, onset and progression of AMD are affected by diet and lifestyle choices. For instance, smoking cigarettes definitely increases your risk of developing AMD. Other foods associated with lower risk of AMD are dark green leafy vegetables, orange and yellow vegetables and fruits: spinach, kale, collard greens, yellow corn, broccoli, sweet potatoes, squash, orange bell peppers, oranges, mangoes, apricots, peaches, honeydew melon, and papaya. Two unifying phytochemicals in this food list are lutein and zeaxanthin, which are also found in red grapes, kiwi fruit, lima beans, green beans, and green bell peppers. Increasing your intake of these foods as part of the Advanced Mediterranean Diet may well help preserve your vision as you age.      
    
Alzheimer’s Dementia
    
Another exciting potential benefit of fish consumption is prevention or delay of Alzheimer’s dementia. Several recent epidemiologic studies have suggested that intake of fish once or twice per week significantly reduces the risk of Alzheimer’s. Types of fish eaten were not specified. No one knows if fish oil capsules are equivalent. For now, I’m sticking with fatty cold-water fish, which I call my “brain food.”
    
Vitamin E supplements may slow the progression of established Alzheimer’s disease; clinical studies show either modest slowing of progression or no benefit. As a way to prevent Alzheimer’s, however, vitamin E supplements have been disappointing. On the other hand, high dietary vitamin E is associated with reduced risk of developing Alzheimer’s. Good sources of vitamin E include vegetable oils (especially sunflower and soybean), sunflower seeds, nuts, shrimp, fruits, and certain vegetables: sweet potatoes, asparagus, beans, broccoli, Brussels sprouts, carrots, okra, green peas, sweet peppers, spinach, and tomatoes. All of these are on your new diet. 

Wine

For centuries, the healthier populations in the Mediterranean region have enjoyed wine in light to moderate amounts, usually with meals. Epidemiologic studies there and in other parts of the world have associated reasonable alcohol consumption with prolonged lifespan, reduced coronary artery disease, diminished Alzheimer’s and other dementias, and possibly fewer strokes. Alcohol tends to increase HDL cholesterol, have an antiplatelet effect, and may reduce C-reactive protein, a marker of arterial inflammation. These effects would tend to reduce cardiovascular disease. Wine taken with meals provides antioxidant phytochemicals (polyphenols, procyanidins) which may protect against atherosclerosis and some cancers. 

What’s a “reasonable” amount of alcohol? An old medical school joke is that a “heavy drinker” is anyone who drinks more than the doctor does. Light to moderate alcohol consumption is generally consi-dered to be one or fewer drinks per day for a woman, two or fewer drinks per day for a man. One drink is 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of 80 proof distilled spirits (e.g., vodka, whiskey, gin). The optimal health-promoting type of alcohol is unclear. I tend to favor wine, a time-honored component of the Mediterranean diet. Red wine in particular is a rich source of resveratrol, which is thought to be a major contributor to the cardioprotective benefits associated with light to moderate alcohol consumption. Grape juice may be just as good—it’s too soon to tell.
    
I have no intention of overselling the benefits of alcohol. If you are considering habitual alcohol as a food, be aware that the health benefits are still somewhat debatable. Consumption of three or more alcoholic drinks per day is clearly associated with a higher risk of breast cancer in women. Even one or two drinks daily may slightly increase the risk. Folic acid supplementation might mitigate the risk. If you are a woman and breast cancer runs in your family, strongly consider abstinence. Be cautious if there are alcoholics in your family; you may have inherited the predisposition. If you take any medications or have chronic medical conditions, check with your personal physician first. For those drinking above light to mod-erate levels, alcohol is clearly perilous. Higher dosages can cause hypertension, liver disease, heart failure, certain cancers, and other medical problems. And psychosocial problems. And legal problems. And death. Heavy drinkers have higher rates of violent and accidental death. Alcoholism is often fatal. You should not drink alcohol if you:
            ■  have a history of alcohol abuse
                or alcoholism
            ■  have liver or pancreas disease
            ■  are pregnant or trying to become
                pregnant
            ■  may have the need to operate
                dangerous equipment or machinery,
                such as an automobile, while under
                the influence of alcohol
            ■  have a demonstrated inability to
                limit yourself to acceptable
                intake levels
            ■  have personal prohibitions due
                to religious, ethical, or other
                reasons. 
    
Cancer

Do you ever worry about cancer? You should. It’s the second leading cause of death. Over 500,000 people die from cancer each year in the United States. One third of people in the United States will develop cancer. Twenty percent of us will die from cancer. About half the deaths are from cancer of the lung, breast, and colon/rectum. Are you worried yet?

According to the American Cancer Society, one third of all cancer deaths can be attributed to diet and inadequate physical activity. So we have some control over our risk of developing cancer. High consumption of fruits and vegetables seems to protect against cancer of the lung, stomach, colon, rectum, oral cavity, and esophagus, although other studies dispute the protective linkage. Data on other cancers is limited or inconsistent. If you typically eat little or no fruits and vegetables, you can start today to cut your cancer risk by up to one half. Five servings of fresh fruits and vegetables a day seems to be the protective dose against cancer. Make it a life-long habit. The benefits accrue over time. Fruits and vegetables contain numerous phytochemicals thought to improve or maintain health, such as carotenoids (e.g., lycopene), lignans, phytosterols, sulfides, isothyocyanates, phenolic compounds (including flavonoids, resveratrol, phytoestrogens, antho-cyanins, and tannins), protease inhibitors, capsaicin, vitamins, and minerals. 
   
In addition to cancer prevention properties, fruits and vegetables provide fiber, which is the part of plants resistant to digestion by our enzymes. The other source of fiber is grain products, especially whole grains. Liberal intake of fiber helps prevent constipation, diverticular disease, hemorrhoids, irritable bowel syndrome, and perhaps colon polyps. Soluble fiber helps control blood sugar levels in diabetics. It also reduces LDL cholesterol levels, thereby reducing risks of coronary heart disease. Whether or not related to fiber, high fruit and vegetable intake may reduce the risks of coronary heart disease and stroke. Legume consumption in particular has been associated with a 10 to 20% lower risk of coronary heart disease, with the effective dose being around four servings per week. 

Fiber and Whole Grains

Processed, refined grain products have much less fiber than do whole grains. For instance, white all-purpose enriched flour has only about one fourth the fiber of whole wheat flour. The milling process removes the bran, germ, and husk (chaff), leaving only the endosperm as the refined product, flour. Endosperm is mostly starch and 10–15% protein. Many nutrients are lost during processing. The germ is particularly rich in vitamins (especially B vitamins), polyunsaturated fatty acids, antioxidants, trace minerals, and phytochemicals. Phytochemicals protect us against certain chronic diseases. Bran is high in fiber and nutrients: B vitamins, iron, magnesium, copper, and zinc, to name a few. Enriched grain products are refined grains that have had some, but certainly not all, nutrients added back, typically iron, thiamin, niacin, riboflavin, and folate. Why not just eat the whole grain? Whole grain products retain nearly all the nutrients found in the original grain. Hence, they are more nutritious than refined and enriched grain products.
    
Liberal intake of high-fiber whole grain foods, as contrasted with refined grains, is linked to lower risk of death and lower incidence of coronary heart disease and type 2 diabetes mellitus. For existing diabetics, whole grain consumption can help im-prove blood sugar levels. Three servings of whole grains per day cut the risk of coronary heart disease by about 25 percent compared with those who rarely eat whole grains. Regular consumption of whole grains may also substantially reduce the risk of sev-eral forms of cancer.

Average adult fiber intake in the United States is 12 to 15 grams daily. Expert nutrition panels and the American Heart Association recommend 25 to 30 grams daily from whole grains, fruits, and vegetables.

The health benefits of the Mediterranean diet likely spring from synergy among multiple Mediteranean diet components, rather than from a single food group or one or a few food items. 

Steve Parker, M.D.

I have a stack of scientific articles I’ve been meaning to review in depth and blog about.  But I have to finally admit I don’t have the time.  Here they are.  Click through for details.

1. Long-term calorie restriction in humans appears highly effective in reducing atherosclerosis risk factors (lab tests) and actual carotid artery atherosclerosis. Only 18 study subjects, however.
2. A very-low-carbohydrate diet improved memory in older adults with mild cognitive impairment over six weeks.  Twenty-three subjects were randomized to either high-carb or very-low-carbohydrate diet.  The low-carbers improved verbal memory performance, lost weight, reduced fasting blood sugar and fasting insulin levels.  Ketone levels were positively correlated with memory performance.
3. A high-fat diet impairs cognitive function and heart energy metabolism in young men.  Sixteen test subjects.  Crossover study design with a five-day high-fat diet deriving 75% of energy from fat, compared to a low-fat diet deriving 23% of energy from fat.  High-fat diet led to impaired attention, speed, and mood.  I’m sure low-carb bloggers have been all over this.  At first blush, it appears they were testing during “induction flu” phase of very-low-carb eating, between days 2 to 7 of a new ketogenic diet.  It takes several weeks to adapt metabolism to running almost entirely on fat rather than standard carbohydrates.  Suspect results would have been different if given time to adapt.
4. Weight-loss with the laparoscopic gastric banding procedure has poor long-term outcome, according to Belgian surgeons reporting on 82 patients.  Four in 10 patients had major complications.  Nearly half of the 82 patients needed to have the bands removed, and six of every 10 required some kind of re-operation.
5. Trust me, you DON’T want age-related macular degeneration.  Women, reduce your risk of ARMD with a healthy lifestyle, including regular exercise, avoidance of smoking,  and by eating abundant plant foods (vegetables [including orange and dark leafy green ones], fruits, and whole grains) and limit foods high in fat, refined starches, sugar, alcohol, and oils.  At least according to these researchers. 
6. Leafy green vegetables and olive oil are linked to reduced heart disease (CHD) in Italian women.  Fruit consumption had no effect.  This is from a subset of the huge EPIC study, following 30,000 women over almost eight years.
7. The Mediterranean diet protects against metabolic syndrome, reducing risk by about a third according to a huge meta-analysis from Greek and Italian investigators.  It works best in Mediterranean countries. 
8. The Mediterranean diet was linked to slower rates of cognitive decline in Chicago residents over the course of almost eight years.  The comparison diet was the Healthy Eating Index-2005.  Of the 3,800 participants, about two-thirds were black.  A Manhattan population showed lower risk of dementia when eating Mediterranean-style.

There ya’ go.  This is better than letting the articles just sit in my briefcase for months on end, eventually to be thrown out.

Steve Parker, M.D.

Ketogenic diets have seen a resurgence in the last two decades as a treatment for childhood epilepsy, particularly difficult-to-control cases not responding to drug therapy.  It works, even in adults.  That’s why some brain experts are wondering if ketogenic diets might be helpful in other brain disorders, such as Alzheimer’s disease and Parkinson’s disease. 

I’ll save you some time and just give you the conclusion of a 2006 scientific article I read: maybe, but it’s way too soon to tell.

The article is called “Neuroprotective and disease-modifying effects of the ketogenic diet,” from researchers at the National Institutes of Health’s National Institue of Neruological Disorders and Stroke.  Sounds promising doesn’t it?

The article goes into detail about how the ketogenic diet might be good for brain health.  Dr. Emily Deans would be very interested in that, but most of my readers not.  Two-and-a-half pages on non-human animal studies, too. 

What is this ”Ketogenic diet” used for epilepsy?

The most common ketogenic diet for childhood epilepsy is the one developed by Wilder in 1921.  It was a popular treatment for epilepsy in the 1920s and 1930s.  Fats provide 80 to 90% of the calories in the diet, with sufficient protein for growth, and minimal carbohydrates.  Since carbs are in short supply, the body is forced to use fats as an energy source, which generates ketone bodies—acetoacetate, acetone, beta-hydroxybutyrate, largely from the liver.

So what?

Not much.  This article may have been written to stimulate future research, and I hope it does.  I just searched PubMed for “ketogenic diet AND Alzheimer” and came up with nothing new since 2006. 

Could the Ketogenic Mediterranean Diet prevent or alleviate Alzheimer’s disease?  At this point, just flip a coin.

Steve Parker, M.D.

Reference: Gasior M, Rogawski MA, & Hartman AL (2006). Neuroprotective and disease-modifying effects of the ketogenic diet. Behavioural pharmacology, 17 (5-6), 431-9 PMID: 16940764

A cocktail of three common B vitamins slowed the rate of brain shrinkage over two years  in elderly patients with mild cognitive impairment, according to researchers at the University of Oxford.

As a hospitalist, I see 10 or 20 brain scans every week.  A healthy 40-year-old brain nicely fills out the allotted space in the skull.  Most 70-year-old brains have an obvious degree of shrinkage.  Those with the most shrinkage typically have worse mental functioning, often diagnosed clinically as dementia, or its precursor, mild cognitive impairment (MCI).

The medical term for brain shrinkage is brain atrophy.  It reflects loss of brain cells or decrease in brain cell size.  I see A LOT of atrophied brains and impaired mental functioning—aka cognition—in the elderly. 

Not everybody with atrophy has mental impairment; healthy brains slowly atrophy with age.  Alzheimer’s disease patients atrophy quickly; MCI patients atrophy at an intermediate rate.  MCI patients converting over the years to Alzheimer’s show a faster rate of atrophy.

Mild cognitive impairment affects 14 to 18% of those over age 70 (five million in the U.S.).  Half of these convert to Alzheimer’s disease or another dementia within five years.  We desperately need a way to prevent or slow that conversion.

That’s why I was excited to see a research report in which brain atrophy was slowed with three simple daily vitamins: folic acid 0.8 mg, B12 0.5 mg, and B6 20 mg.  The investigators will report later on whether the vitamins helped prevent mental decline.

These three vitamins are involved in homocysteine metabolism; they decrease blood levels of homocysteine.  Read elsewhere if you want the boring details. 

Methodology

Oxford area participants were at least 70 years of age and had mild cognitive impairment but not dementia.  Blood homocysteine levels were drawn periodically.  Participants were randomized to take either placebo (83 subjects) or the daily vitamins (85 subjects) for two years.  MRI scans were done periodically to determine brain volume.  Tests of mental functioning were done periodically.  More subjects were in the study at the outset but some dropped out and others didn’t have technically adequate MRI scans.

Results

After adjustment for age, the annual rate of brain atrophy was 30% less in the vitamin group compared to placebo.

For the placebo group, the rate of brain atrophy was clearly related to baseline homocysteine levels: higher homocysteine, faster atrophy.

Although the study was not powered to detect an effect of treatment on cognition (findings to be reported separately), in a post hoc analysis, we noted that final cognitive test scores were correlated to the rate of atrophy.

Atrophy appears to be a major determinant of cognitive decline in this population.

There were no significant safety issues and no differences in adverse events between the groups.

The vitamin group lowered homocysteine levels by 32% compared to placebo.

Reduction in brain shrinkage rate was best in those with a higher baseline homocysteine level (over 13 micromol/L); those with the lowest baseline levels (<9.5 micromol/L) showed no effect of vitamin therapy.  [In the U.S., 13% of those over 60 have concentrations over 13 micromol/L, whereas the median is 10 micromol/L.]

Comments

Although this is small study, I’m excited about the future clinical implications.  The results need to be replicated.  I can’t wait to hear from this group regarding the details of mental functioning tests.  If preservation of brain function or other practical benefits don’t accompany a slower rate of atrophy , it’s no use taking the vitamins.

A 2008 study found no clinical benefit with a similar vitamin mix in Alzheimer’s patients with mild to moderate disease.  In other words, the rate of mental decline was no different than the placebo group.  Average homocysteine level was 9.16 micromole/L and fell by 30% during the 18-month-long study.  Even those with the highest homocysteine levels showed no benefit.  Perhaps B vitamins need to be started much earlier in the disease process to be effective.

The time may come where we screen all 60-year-olds for above-average homocysteine levels, starting them on the vitamin cocktail.

One caveat, however.  Ten years ago doctors were quite excited about preventing heart disease events (e.g., heart attacks, cardiac deaths) and strokes in people with high homocysteine levels.  We knew that high levels were associated with cardiac events and strokes, and we knew the B vitamins would lower the blood levels.  We learned a couple years ago that B vitamin therapy actually didn’t help heart patients or those at high risk for heart disease.  Nor do the vitamins prevent strokes.  [If you’re a heart patient still taking Foltx, ask your cardiologist if it’s OK to stop it now.]

Steve Parker, M.D.

References: 
Smith, A., Smith, S., de Jager, C., Whitbread, P., Johnston, C., Agacinski, G., Oulhaj, A., Bradley, K., Jacoby, R., & Refsum, H. (2010). Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial PLoS ONE, 5 (9) DOI: 10.1371/journal.pone.0012244

Aisen, P.S., et al.  High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial.  Journal of the American Medical Association, 300 (2008): 1,774-1,783.

Contrary to popular belief among the experts, type 2 diabetes is not one of the causes of Alzeimer dementia.  They may indeed be associated with each other, but that’s not causation.

An oft-repeated theory from Gary Taubes 2007 masterpiece, Good Calories, Bad Calories, is that many of the chronic diseases of modern civilization, including Alzheimer disease, are caused by abnormal blood sugar and insulin metabolism.  Especially high insulin levels induced by a diet rich in refined carbohydrates.  If that’s the case, you’d expect to see a high prevalence of Alzheimer disease in older type 2 diabetics.

Dr. Emily Deans (psychiatrist) has been considering this issue recently at her Evolutionary Psychiatry blog.

The brains of Alzheimer patients, under a microscope, are characterized by many senile plaques (aka neuritic plaques) and neurofibrillary tangles.  That’s the gold standard for diagnosis.  Nevertheless, brain biopsies are rarely done to diagnose Alzheimer disease in living patients, and even autopsies after death are rare.  The diagnosis usually is clinical, based on ruling out other illnesses, etc.

Nearly all the studies associating diabetes with Alzheimers disease (and other dementias) are observational or epidemiologic.  [The exception is the Honolulu-Asia Aging Study.]  Establishing an association is helpful in generating theories, but establishing causation is the goal.  At least five studies confirm an association.

Neurology this year reported findings of Japanese researchers who examined the brains of 135 people who died between 1998 and 2003.  They lived in Hisayama, a town with an incredibly high autopsy rate of 74%.  These people before death had undergone an oral glucose tolerance test.  Their insulin resistance was calculated on the basis of fasting glucose and fasting insulin (HOMA-IR).  None of them showed signs of dementia at the time of study enrollment in 1988.

What Did They Find?

Twenty-one of the 135 subjects developed Alzheimer-type dementia.  The investigators don’t say if the diagnosis was based on the brain examination, or just a clinical diagnosis without a brain biopsy or autopsy.  How this got beyond the article reviewers is beyond me.  [If I’m missing something, let me know in the comments section below.]  It must be a clinical diagnosis because if you don’t act demented, it doesn’t matter how many senile plaques and neurofibrillary tangles you have in your brain.

Senile plaques, but not neurofibrillary tangles, were more common  in those with higher levels of blood sugar (as measured two hours after the 75 g oral glucose dose), higher fasting insulin, and higher insulin resistance.  People with the APOE epsilon-4 gene were at even higher risk for developing senile plaques.

The researchers did not report whether the subjects in this study had been diagnosed during life with diabetes or not.  One can only hope those data will be published in another paper.  Why make us wait?

Average fasting glucose of all subjects was 106 mg/dl (5.9 mmol/l); average two-hour glucose after the oral glucose load was 149 mg/dl (8.3 mmol/l).  By American Association of Clinical Endocrinologists criteria, these are prediabetic levels.  Mysteriously, the authors fail to mention or discuss this.  [I don’t know if AACE criteria apply to Japanese.]  Some of these Japanese subjects probably had diabetes, some had prediabetes, others had normal glucose and insulin metabolism.

As with all good research papers, the authors compare their findings with similar published studies.  They found one autopsy study that tended to agree with their findings (Honolulu) and three others that don’t (see references below).  In fact, one of the three indicated that diabetes seems to protect against the abnormal brain tissue characteristic of Alzheimer disease.

Botton Line

Type 2 diabetes doesn’t seem to be a cause of Alzheimer disease, if autopsy findings and clinical features are the diagnostic criteria for the disease.

If we assume that type 2 diabetics have higher than normal blood sugar levels and higher insulin levels for several years, then hyperglycemia and hyperinsulinemia don’t cause or contribute to Alzheimer dementia.  Myth busted.  [I hope that’s not copyrighted by the “Myth Busters” TV show.]

Type 2 diabetes is, however, linked with impaired cognitive performance, at least according to many of the scientific articles I read in preparation for this post.  So type 2 diabetics aren’t in the clear yet.  It’s entirely possible that high blood sugar and /or insulin levels cause or contribute to that.  [Any volunteers to do the literature review?  Best search term may be “mild cognitive impairment.”]

Type 2 diabetes is associated with Alzheimer disease, but we have no proof that diabetes is a cause of Alzheimers.  Nor do we have evidence that high blood sugar and insulin levels cause Alzheimer disease.

Alzheimer disease is a major scourge on our society.  I’d love to think that carbohydrate-restricted eating would help keep blood sugar and insulin levels lower and thereby lessen the devastation of the disease.  Maybe it does, but I’d like to see more convincing evidence.  It’ll be years before we have a definitive answer.

For now, we have evidence that the Mediterranean diet seems to 1) protect againstAlzheimers and other dementias, 2) prevent some cases of type 2 diabetes, and 3) reduce the need for diabetic medications in diabetics.

For more information on practical application of the Mediterranean diet, visit Oldways and the Advanced Mediterranean Diet website.

Steve Parker, M.D.

References:

Matsuzaki T, Sasaki K, Tanizaki Y, Hata J, Fujimi K, Matsui Y, Sekita A, Suzuki SO, Kanba S, Kiyohara Y, & Iwaki T (2010). Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study. Neurology, 75 (9), 764-70 PMID: 20739649

Heitner, J.,  et al. “Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects: a retrospective postmortem immunocytochemical and histofluorescent study.” Neurology, 49 (1997): 1306-1311.  Autopsy study, No. of subjects not in abstract. They looked for senile plaques and neurofibrillary tangles, etc. The title says it all.

Beeri,  M.S., et al. “Type 2 diabetes is NEGATIVELY [emphasis added] associated with Alzheimer’s disease neuropathology.” J. Gerontol A. Biol Sci. Med. Sci. 60 (2005): 471-475.  385 autopsies. The title again says it all.

Arvanitakis, Z., et al. “Diabetes is related to cerebral infarction but NOT [emphasis added] to Alzheimers disease pathology in older persons.”  Neurology, 67 (2006): 1960-1965. Autopsy study of 233 Catholic clergy, about 50:50 women:men.

Italian researchers reviewed the medical/nutrition literature of the last three years and confirmed that the Mediterranean diet 1) reduces the risk of death, 2) reduces  heart disease illness and death, 3) cuts the risk of getting or dying from cancer, and 4) diminishes the odds of developing dementia, Parkinsons disease, stroke, and mild cognitive impairment.

These same investigators published a similar meta-analysis in 2008, looking at 12 studies.  Over the ensuing three years (as of June, 2010), seven new prospective cohort studies looked at the health benefits of the Mediterranean diet.  The report at hand is a combination of all 19 studies, covering over 2,000,000 participants followed for four to 20 years.  Nine of the 19 Mediterranean diet studies were done in Europe.

The newer studies, in particular, firmed up the diet’s protective effect against stroke, and added protection against mild cognitive impairment.

So What?

The Mediterranean diet: No other way of eating has so much scientific evidence that it’s healthy and worthy of adoption by the general population.  Not the DASH diet, not the “prudent diet,” not the American Heart Association diet, not vegetarian diets, not vegan diets, not raw-food diets, not Esselstyne’s diet, not Ornish’s diet, not Atkins diet, not Oprah’s latest diet, not the Standard American Diet, not the  . . . you name it. 

Not even the Low-Carb Mediterranean Diet.

Just as important, the research shows you don’t have to go full-bore Mediterranean to gain a health and longevity benefit.  Adopting  just a couple Mediterranean diet features yeilds a modest but sigificant gain.  For a list of Mediterranean diet components, visit Oldways or the Advanced Mediterranean Diet website. 

Steve Parker, M.D.

Reference:  Sofi F, Abbate R, Gensini GF, & Casini A (2010). Accruing evidence about benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. The American journal of clinical nutrition PMID: 20810976

I blogged about a study by Gu et al on April 30, 2010, that found significantly lower incidence of Alzheimer dementia in people in Manhattan who followed this dietary pattern:

• relatively high consumption of salad dressing, nuts, fish, tomatoes, fruits, dark green leafy vegetables, and cruciferous  vegetables
• relatively low consumption of poultry, red meat, butter, and high-fat dairy

About the same time, a National Institutes of Health expert panel pooh-poohed the possibility that diet had any effect one way or the other on Alzheimer’s. 

Why does this matter?  Five million U.S. adults have Alzheimer dementia already, and it’s going to get much worse over the coming decades.

A June, 2010, issue of Journal of the American Medical Association has a commentary by two doctors (Martha Morris, Sc.D., and Christine Tangney, Ph.D.), experts in the field of nutrition.  Here’s their explanation of the NIH panel’s negative findings:

Many of the inconsistencies among studies of dietary factors can be attributed to the complexity of nutrition science and the omission of nutrition expertise in the design and analysis of both epidemiological and randomized controlled trials.

Morris and Tangney think the findings of Gu et al are valid, confirming prior studies showing benefit to diets high in vitamin E (from food) and low in saturated fat from animals.  They point out that the animal foods may simply be displacing beneficial nutrients in other foods, rather than directly causing harm.

Until we have further data, anyone at risk for Alzhiemer’s may be better off following the dietary pattern above, or the Mediterranean diet.  The two are similar.

Steve Parker, M.D.

Disclaimer:  All matters regarding your health require supervision by a personal physician or other appropriate health professional familiar with your current health status.  Always consult your personal physican before making any dietary or exercise changes. 

Reference: Morris, M., & Tangney, C. (2010). Diet and Prevention of Alzheimer Disease JAMA: The Journal of the American Medical Association, 303 (24), 2519-2520 DOI: 10.1001/jama.2010.844