Resveratrol and Alzheimer’s disease
Zinc and pregnancy
Blood fats and arterial stiffness
Healthier fat intake may extend life
Vitamin E reduces cellular aging
Resveratrol is a polyphenol found in red and purple grapes (mostly in the skin), cranberries, blueberries, peanuts, and, most popularly, in red wine. A glass of wine can contain about 200 to 2000 micrograms (mcg), equal to 0.2 to 2.0 milligrams (mg). Peanut butter has about 5 mcg per gram (gm), and a tablespoon is about 16 gms, with about 105 calories, so 2 tablespoons provides about 160 mcg of resveratrol
New information suggests that resveratrol may help Alzheimer’s disease patients. A randomized, placebo-controlled, double-blind study included 119 subjects with mild to moderate Alzheimer’s disease. Half were given 500 mg orally once daily, with the dose increasing by 500 mg every 13 weeks. The study lasted 52 weeks. Resveratrol and its major metabolites were measurable in the blood and cerebrospinal fluid (CSF).
They measured amyloid beta 40 (Abeta40) in the plasma and in the CSF. Abeta40 declines in both plasma and CSF as the Alzheimer’s dementia progresses. They also used MRI studies to evaluate the brain volume. The resveratrol was safe and generally well tolerated, although some patients had nausea or diarrhea.
At the end of the 52 weeks, the Abeta40 levels in both plasma and CSF declined more in the placebo group than in the resveratrol group. The researchers noted that the brain volume went down more with resveratrol than with placebo. They speculated that the decrease in brain volume might be due to a decrease in inflammation induced by the treatment. (Turner RS, et al., A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015 Oct 20;85(16):1383-91.)
For reference, the amount of resveratrol that they used was equivalent to the amount that would be found in 1000 glasses of red wine, so it is not related to dietary levels. However, when treating a devastating disease such as Alzheimer’s, it is worth trying doses that are higher than those found in food, as long as they are safe. Supplements are available with anywhere from 30 to 250 mg of resveratrol.
Zinc is a trace mineral required in the diet. It is a cofactor in up to 300 enzyme systems. It is required for growth and development, both prenatally and postnatally, and is essential for immune function, wound healing, and antioxidant activity. It is a key nutrient in prostate gland function, reproductive organ growth, and brain function, and was shown in the AREDS study to be important for retinal health. Zinc deficiency has been associated with major depressive disorder.
A recent study from China shows the importance of adequate zinc for healthy pregnancy tcomes. Researchers evaluated the birth records of 3081 mothers with detailed birth records that included serum samples analyzed for zinc levels. Among these women, 169 preterm births were identified. The women were divided into thirds based on their serum zinc levels, low (less than 76.7 mcg/dL), medium (76.7-99.6 mcg/dL), and high (above 99.7 mcg/dL).
Preterm births incidence was 7.3 percent for those with low zinc, and 6.0 percent for those with medium zinc levels. Women with high zinc levels had just a 3 percent incidence of preterm births. (Wang H, et al., Maternal serum zinc concentration during pregnancy is inversely associated with risk of preterm birth in a Chinese population. J Nutr. 2016 Jan 27. pii: jn220632. [Epub ahead of print])
This shows the importance of comprehensive nutrition for healthy pregnancies. Adequate zinc levels were most helpful in the first trimester of pregnancy.
Dietary sources of zinc include meats and shellfish, but healthier sources are whole grains, pumpkin seeds, sesame seeds, beans, and nuts, such as almonds. Most multivitamin supplements have basic amounts of zinc that would often be adequate, and vision formulas routinely include it. High doses of zinc taken for the long term can cause copper deficiency. Zinc lozenges may help with sore throats and colds.
Polyunsaturated fatty acids (PUFA) are found in vegetable oils, such as corn, soybean, safflower, canola, and peanut oils, and they contain mainly omega-6 fatty acids. They remain liquid even in the refrigerator. They don’t solidify as saturated fats do (even at room temperature). This means that fish that live in cold water need to have more polyunsaturated fats in their tissues so that they can remain flexible and swim around. Their most important polyunsaturated fats for human health are omega-3 oils, which have a lot of physiological benefits, including anti-inflammatory effects, inhibition of platelet stickiness, reduction of the risk of cardiovascular disease, help with congestive heart failure, lowering blood pressure and triglycerides, and help with asthma.
With aging, arterial walls, which are composed of endothelial cells, muscle, elastin, and collagen and are normally very flexible, tend to get stiff, particularly if they are stressed by hypertension and inflammation. Arterial stiffness is an indicator of cardiovascular disease risk. As the arteries stiffen, the heart has to work harder to pump blood. Stiffness is indicated by pulse wave velocity and the difference between the systolic and diastolic blood pressures. A lower pulse wave velocity is associated with greater arterial flexibility.
A new study shows that higher serum levels of omega-3 fatty acids are associated with a lower pulse wave velocity. Researchers gathered data from a subgroup in an Icelandic population-based study. They had 501 adults 70 to 80 years old, of whom 46 percent were men. They assessed plasma fatty acids at the start of the study, and fish oil intake was estimated at three time points – early life (14 to 19 y), midlife (40-50 y), and late life (66-96 y), by means of a validated food-frequency questionnaire. The omega-3 fatty acids they measured were eicosapentaenoic (EPA) and docosahexaenoic (DHA). They followed the subjects for an average of 5.2 years.
They found that higher plasma omega-3 fatty acids were associated with a lower pulse wave velocity, with EPA having a greater association than either total omega 3 fatty acids or DHA alone. In contrast, higher plasma levels of omega-6 fatty acids (much of it from highly processed foods) were associated with a greater risk of arterial stiffness. Aside from fish, omega-3 fatty acids (alpha-linolenic acid or ALA) are found in flaxseeds, walnuts, soybeans, and chia seeds. However, these also come with omega-6 fatty acid, which are essential but commonly overabundant in the Western diet from highly processed oils used in manufactured foods. Remember from my last newsletter that ALA has to be converted by enzymes into EPA and DHA, a process that is sometimes limited by age and illness. Unlike plasma levels, the questionnaire about fish oil intake at different stages of life did not show any association with arterial stiffness measures. This might be due to poor recall of dietary intake by the participants. (Reinders I, et al., Higher plasma phospholipid n-3 PUFAs, but lower n-6 PUFAs, Are associated with lower pulse wave velocity among older adults. J Nutr. 2015 Oct;145(10):2317-24.)
Consuming oily fish such as wild salmon and sardines can provide significant omega-3 oils. Supplements are available with various combinations of EPA and DHA. For vegetarians, flax and chia seeds are probably the most abundant sources of omega-3 oils. I often use organic flaxseed oil in salad dressing or on a baked potato, or I will put a little on my soba (buckwheat) noodles. I also take a fish oil supplement containing 600 mg of EPA/DHA in each of two capsules.
Fat intake has practical implications for health and longevity. Poor choices can lead to an increased risk of heart disease (CHD). The problem is no longer limited to the so-called Western Diet, as this collection of highly processed and fast foods has now spread virtually worldwide. A new study from researchers at Tufts University’s Friedman School of Nutrition reveals a correlation between polyunsaturated fatty acid (PUFA) intake, saturated fat acids (SFA) intake, and trans fatty acid (TFA) intake and mortality from CHD.
They used country-specific dietary surveys, food availability data, and for TFA, industry reports on fats/oils and packaged foods. They evaluated the potential causative effects of fats on CHD mortality derived from meta-analyses of prospective studies and mortality rates from the 2010 Global Burden of Diseases study. With this information, they estimated that the non-optimal intake of omega-6 PUFA (either too much or too little, but primarily too little) was associated with an extra 711,800 deaths from CHD annually. Non-optimal intake of SFA (too much, as this is not an essential fatty acid) was associated with 250,000 extra deaths, and TFA excess was associated with 537,200 extra deaths. (Wang Q, ET AL., Impact of nonoptimal intakes of saturated, polyunsaturated, and trans fat on global burdens of coronary heart disease. J Am Heart Assoc. 2016 Jan 20;5(1).)
During the 20-year period that they analyzed, deaths from too little PUFAs declined by 9 percent, while deaths from too much saturated fat declined by 21 percent (reflecting increases in PUFA intake where it was too low and reduction of SFA intake where it was too high). However, deaths from TFA intake increased by 4 percent, driven by increases in low- and middle-income countries – this reflects the increasingly pervasive nature of processed foods, as TFA barely occur in nature (it occurs when unsaturated fats are artificially saturated (hydrogenated) during processing).
A healthful diet is naturally quite low in all fats, and particularly saturated fats. When Dennis Burkitt, M.D., studied the native African diet in the 1950s, he found they had virtually no heart disease, strokes, hypertension, colon cancer, or diabetes. The staples of their diet were potatoes, bananas, corn meal, and beans. He attributed their health to the high fiber content of their diet, but that is not the only benefit from such a diet.
I don’t shy away from all oils, and I include flaxseed oil and olive oil in my diet, but I do not overdo it, as these are extracted foods, rather than the whole foods that I prefer. I suggest cooking with a small amount of olive oil, and using flaxseed oil in salad dressings (it is very fragile and should never be cooked). I also eat coconut and use some coconut oil in baked goods, but these are a small part of my diet. Whole grains and beans contain some essential PUFAs, and I also include walnuts, almonds, cashews, sesame seeds, and sunflower seeds in my diet. These are all good sources of PUFAs. With healthful dietary choices, you do not need to add any oils for health, although you might want to include some for culinary purposes or taste. Healthful diets typically derive about 15-20 percent of their calories from fat and 10 to 20 percent from protein. Most of the rest is from complex carbohydrates (but very little from simple carbs, such as sugar and white flour). Complex carbs include whole grains, beans, vegetables, potatoes, sweet potatoes, and root vegetables. I also eat a lot of fruit for the phytochemicals and fiber, but I primarily choose all of my foods for pleasure.
Vitamin E is important as an antioxidant that reduces oxidative stress-induced cellular damage. This oxidative damage contributes to the progression of aging. It is hard to do clinical aging studies because they would have to go on for far too long and be extremely expensive, so we need to extrapolate based on information from other research. Researchers used cultured endothelial cells and fibroblasts and treated them with different concentrations of vitamin E for different lengths of time.
They used several methods to assess the number of aged cells, including chemical tests and stains. Both short-term and long-term treatment with vitamin E led to a decrease in the number of aged (senescent) cells. The longer treatment with vitamin E was significantly better at reducing senescence than the short term treatment. This information strongly suggests that long term treatment with vitamin E can slow the aging process, and this accords with some other research on antioxidants. (La Fata G, et al., Vitamin E supplementation delays cellular senescence in vitro. Biomed Res Int. 2015;2015:563247. doi: 10.1155/2015/ 563247. Epub 2015 Nov 3.)
Vitamin E occurs in the diet in small amounts in sources such as sunflower seeds, almonds, spinach, Swiss chard, avocado, and peanuts. However, it is difficult to get anywhere near the amounts that have been used in clinical research. Daily doses ranging from 200 IU to 2000 IU have shown benefits in Alzheimer’s disease, Parkinson’s disease, rheumatoid arthritis, claudication (leg pain with exercise), heart disease, and immune function. This study used synthetic vitamin E (dl-alpha tocopherol), but I recommend the more effective natural vitamin E (d-alpha, not dl) as well as the other forms of vitamin E, beta, gamma, and delta, but especially the gamma-tocopherol. I take a capsule high in gamma tocopherol (750 mg) plus 200 IU of d-alpha, and 290 mg of mixed beta and delta tocopherols.