Fountain of Youth

Introduction:

This information includes a collection of observational research, supplements, and lifestyle habits which have resulted in mortality reduction. This data focuses on topics potentially useful in reducing the risk of both mortality and the major causes of death using mainly non-pharmacological methods. The research included here includes a collection of data relevant to mortality reduction. According to the Centers of Disease Control as of 2010, the top 15 causes of death in the United States include heart disease, cancer, chronic lung disease, stroke, accidents, Alzheimer’s disease, diabetes mellitus, kidney disease, influenza/pneumonia, suicide, sepsis, chronic liver disease, hypertension, Parkinson’s disease, and aspiration pneumonia. This information will be updated and reinforced on a continual basis as new data becomes available.

Reducing risk of mortality in heart disease:

The American Heart Association (AHA) and ideal cardiovascular health:

The AHA explained ideal cardiovascular health should be obtained by targeting 7 behaviors that reduce the likelihood of cardiovascular disease or stroke. They include 4 core behaviors—no smoking, a normal body mass index (BMI), engaging in physical activity, and eating healthfully—and meeting at least 3 of the following criteria: cholesterol lower than 200 mg/dL, blood pressure lower than 120/80 mm Hg, not having diabetes, or being free of heart disease. To assess the effects of meeting these targets on risk of death from cardiovascular disease, Artero and colleagues looked at data from the Aerobics Longitudinal Study, conducted in 11,993 patients between Oct. 9, 1987 and March 3, 1999. The authors found that those who met 3-4 of AHA’s “Simple Seven” heart-health criteria had a 55% lower risk of cardiovascular mortality than those who met no more than 2 of those practices over about 11 years. It was 63% lower for those who fulfilled five to seven of the ideal criteria compared with those with the lowest scores. The overall prevalence of ideal cardiovascular health was extremely low in this middle-aged cohort, with only 0.2% of patients meeting all 7 criteria. (1)

U.S. Preventive Services Task Force (USPSTF) aspirin recommendations:

For the use of aspirin in prevention (45):

Aspirin dosage: According to the USPTF, the ideal dose of aspirin is not known, but a dose of 75 mg per day appears as effective as higher doses and may have less risk of gastrointestinal bleeding. Men benefit from aspirin for the prevention of cardiovascular disease.

Men younger than 45 years: For myocardial infarction prevention in men younger than 45 years the USPSTF recommends against the use of aspirin since the benefit for prevention of cardiovascular events are small.

Men age 45 to 79 years: The U.S. Preventive Services Task Force (USPSTF), strongly recommends the use of aspirin when the potential benefit due to a reduction in myocardial infarctions is more beneficial than the potential harm due to gastrointestinal hemorrhage.

Men and Women 80 years of age and older: According to the U.S. Preventive Services Task Force (USPSTF), there is insufficient evidence to determine the risk verses benefit of taking aspirin by men and women over 79 years of age for the prevention of cardiovascular disease.

Aerobic exercise and coronary artery disease:

Aerobic exercise (with a cardiac rehab program if required) reduces mortality in coronary artery disease. A systematic review and meta-analysis of randomized controlled trials by Taylor et al found that exercise based cardiac rehabilitation reduces all cause and cardiac mortality and improves a number of cardiac risk factors in patients with coronary heart disease according to this meta-analysis of 48 randomized controlled trials (RCTs) (8940 patients, mean age 55 y). Intervention duration ranged from 0.25–30 months and follow up was between 6–72 months. Patients who received exercise-based cardiac rehab had a significant reduction in all cause mortality of 20% and cardiac mortality of 26% than did patients who received usual care. Groups did not differ for rates of non-fatal heart attack (odds ratio [OR]= 0.79), coronary artery bypass grafting (OR=0.87), or percutaneous coronary intervention (OR=0.81). Cardiac rehabilitation was associated with significant reductions in total cholesterol of 0.37 mmol/L and triglyceride concentrations by 0.23 mmol/L; no significant differences were seen in low ‘bad’ or high-density ‘good’ lipoprotein concentrations. Systolic blood pressure was significantly reduced by 3.2 mm Hg. A significant 36% reduction in patient smoking was reported with cardiac rehabilitation. (2)

Nine lifelong cross-country skiers, with a mean age of 81 years and a history of aerobic exercise and participation in endurance events throughout their lives, were examined to determine whole body aerobic capacity and myocellular markers of oxidative metabolism. A cycle test was used to measure aerobic capacity (VO2 max) and a resting vastus lateralis muscle biopsy was used to measure oxidative enzymes associated with muscle health. Six age-matched, healthy, untrained men were used as a comparison. Results indicated that the athletes had a higher absolute (2.6 vs. 1.6 L•min(-1))  and relative (38 vs. 21 ml•kg(-1)•min(-1))  aerobic capacity, heart rate (160 vs. 146 b•min(-1)), and final workload (182 vs. 131 watts). Among athletes, muscle oxidative enzymes were 54% (citrate synthase) and 42% (βHAD) higher. In summary, compared to their counterparts, the life long athletes had better cardiovascular and skeletal muscle health that was associated with lower risk for disability and mortality. (3)

Alcohol use reduces risk of cardiovascular mortality with light to moderate use:

The ideal amount of alcohol consumption in order to obtain benefits of reduced risk for a number of disease states appears to be 2-4 drinks per day for men and 1-2 drinks per day for women. (4)

Drinking alcohol has a protective effect on cardiovascular disease according to a study in Australia. Men who consumed light-to-moderate amounts of alcohol at 3–4 or 5–7 days per week had decreased risks of myocardial infarction and ischemic stroke compared with men who consumed alcohol less than once per week. Moderate alcohol drinking decreases the risk of cardiovascular disease by about 25%, which is linked to a decrease in the total cardiovascular disease burden in Australia of 4.7%. In Australia, 34% of the total number of deaths in 2008 were from cardiovascular disease and in 2003, it was 18% of the overall burden of disease (coronary heart disease and stroke contributed over 80% of this burden). (5)

A study done in Copenhagen, Denmark followed 6051 men and 7234 women between 30 and 70 years old. The relative risk of cardiovascular mortality was significantly less for those who had a low to moderate intake of wine. It was found that beer intake did not change mortality risk much and that drinking spirits increased mortality. (6)

Alcohol intake may increase good cholesterol (HDL). It is believed that HDL increases from alcohol beverages are responsible for 50% of the protective effect from coronary artery disease. The other 50% level of protection may be due to polyphenols in red wine which inhibit platelet aggregation. (7)

Beta-carotene in food vs. supplements and heart disease:

Intake of vegetables containing beta carotene was associated with a lower risk of cardiovascular mortality and with a lower risk for all causes of death but no benefit was seen with taking beta-carotene supplements. Greenberg ER et al tested beta carotene levels in subjects prior to being randomized to take beta carotene supplements. Subjects with an intial beta carotene level of 0.34 to 0.52 umol/L had a 43% less risk of death from cardiovascular disease when compared to subjects with the lowest intial beta carotene levels of under 0.21 umol/L. Those subjects with an intitial beta carotene level of over 0.52 umol/L had a lower risk of death from all causes. There was no reduced risk of disease or mortality benefit in subjects who took beta carotene supplements in pill form. (8)

Beta-carotene supplements are not advised among healthy individuals, unless they suffer from or are at risk of vitamin A deficiency. Beta-carotene supplementation results in a greater increase of beta-carotene blood concentration than beta-carotene rich foods. A 20 mg/d supplement of beta-carotene can result in blood concentrations high enough to increase a patient’s risk of lung cancer, while the same quantity obtained from foods was not associated with lung cancer risk. Additionally, 30 mg/d of beta-carotene supplement was associated with blood concentrations 5 times greater than that of 29 mg/d of beta-carotene from carrots. The consumption of 5 or more daily servings of fruits and vegetables is recommended by “National Cancer Institute’s Five-A-Day for a Better Health program” and “Canada’s Food Guide for Healthy Eating.” Eating a variety of 5 fruits and vegetables per day provides the individual with about 5.2 to 6 mg/day of food based beta-carotene. This allows plasma carotenoid levels to rise above a range represented in studies which were associated with a lower risk of coronary heart disease and all-cause mortality compared to those with a lower food based carotenoid levels. (9)

The Beta-Carotene and Retinol Efficacy Trial (CARET), showed that among 18,314 men and women who smoked heavily or were exposed to asbestos, daily intake of 30 mg (100,000 IU) of beta-carotene and 25,000 IU vitamin A failed to decrease the risk of heart disease. The study was stopped early because it showed that beta-carotene/vitamin A takers who were heavy smokers, ex-smokers or asbestos workers were showing a 28% increased risk of lung cancer in smokers (versus placebo) and a 17% more likely chance of dying, mostly of lung cancer or heart disease.  Results of a 6-year follow-up of study participants showed that compared to the placebo or no intervention group, participants who had taken the intervention had a 12% and 8% increase in relative risk of lung cancer and all-cause mortality among the intervention group, respectively. Researchers also found that after the intervention was stopped relative risk of cardiovascular disease mortality dropped and there was no difference in risk between the two groups. Finally, they found that women were more affected by the supplements with a larger relative risk of cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males. (10)

According to Martini et al in the University of Minnesota Cancer Prevention Research Unit Feeding Studies, an intake of 5 mg per day of beta carotene was required to establish beta carotene levels to a plasma level of 0.37 umol/L. When food based beta carotene was consumed in the form of about 1.5 cups of carrots, and about 0.9 cups of spinach which equated to just over 42 mg of beta-carotene per day, levels increased to 0.83 umol/L. (11)

Beta-carotene in foods: For a breakdown of concentration of beta-carotene in foods, please see: Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. This may be accessed at: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w321.pdf and http://www.nal.usda.gov/fnic/foodcomp/Data/HG72/hg72_2002.pdf

A meta-analysis that included 78 randomized clinical trials was conducted to determine the relationship of oral antioxidant supplementation (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) and mortality. Mean duration of supplementation was 3 years. When all of the trials were combined, and the analysis that is typically used when similarity is present was conducted (fixed-effect model), antioxidant use did slightly increase mortality. When the trials with low risks of bias were considered, the patients consuming the antioxidants had a 4% higher risk of death compared to those taking placebo or no intervention (relative risk [RR]=1.04). The increased risk of mortality was significantly associated with use of beta-carotene (death rate: 13.8% on supplement vs 11.1% on placebo; RR=1.05) and vitamin E (12.0% vs 10.3%; RR=1.03) and possibly vitamin A, though the relationship was not significant with a 14.0% death rate among those taking vitamin A compared to a 13.6% death rate among placebo subjects. The current evidence does not support the use of these antioxidant supplements in the general population or in patients with various diseases. (12)

The studies mentioned thus far on beta-carotene suggest a lower risk of mortality stems from beta carotene intake from food sources but not beta-carotene supplements. The benefit may also come from other substances in the vegetable food source and not necessarily the beta carotene itself.

Vitamin D and heart disease:

Investigators followed a total of 1,194 men over a median duration of 12.7 years in this longitudinal study looking at the link between blood levels of vitamin D and mortality. They looked at vitamin D levels and cardiovascular-related as well as all cause mortality. There was a clear U-shaped curve when looking at the relationship between vitamin D levels and all-cause mortality along with cancer-related mortality, meaning the risk of mortality was significantly increased at both low and high blood levels of vitamin D. In this study, the range with the lowest mortality was about a vitamin D concentration of 24 to 34 ng/ml (60 to 85 nMol/L), which approximately translates to a vitamin D dose of 2000 IU/d. In general, the biggest drop in overall death rates were seen when subjects went from being vitamin D deficient to reaching adequate levels. However, too much vitamin D translated into a gradual increase of mortality rate with cancer deaths rising significantly for the highest levels of vitamin D intake but no increase in cardiovascular mortality was seen. There was a sharp drop in cardiovascular related death rates as study participants went from being vitamin D deficient to approaching a level of 26 ng/ml. At this point there was a leveling off with no added benefit or increase in mortality seen with higher vitamin D levels. Men with low concentrations of vitamin D had a higher cardiovascular mortality. Overall mortality was increased by 50–60% among subjects in the lowest 10% and highest 5% of the vitamin D distribution, whereas cardiovascular mortality was increased only in the bottom 10%. The ideal vitamin D dose according to findings in this study is 2000 IU/d. (13)

Vitamin D is important for reducing the risk of heart disease. A report by the Institute of Medicine (IOM) and the Endocrine Society’s Clinical Practice Guidelines tripled the amount of vitamin D required for most children and adults. The Endocrine Society’s Clinical Guidelines for vitamin D concluded that vitamin D deficiency be defined as a 25(OH)D < 20 ng/ml, insufficiency as a 25(OH)D of 21–29 ng/ml and sufficiency as a 25(OH)D of 30–100 ng/ml. For preventing and treating vitamin D deficiency the Guidelines recommended vitamin D intake should be: children < 1 y 400-1,000 IU/d, children 1-18 y 600-1,000 IU/d and adults 1,500-2,000 IU/d to maintain 25(OH)D concentrations of 40–60 ng/ml.  Upper limits of vitamin D intake were also set as follows: 2000 IU/day for children up to age 1 year; 4000 IU/day for children aged 1 – 18 years, and up to 10,000 IU/day for adults aged 19 years and older. The IOM report concluded that dietary and supplemental vitamin D intake is adequate to satisfy both children and adult, but their study suffered from serious flaws. A study (Moore et al) suggests that neither children nor adults in the US are obtaining the new RDA for vitamin D. Among women vitamin D intake from food was 156–208 IU/d and with supplements 244–324 IU/d. For men, corresponding values were 208–320 IU/d and 308–392 IU/d. There is no evidence that there is a downside to increasing vitamin D intake in children and adults, with the exception of those with chronic granuloma forming disorder or lymphoma in which high vitamin D levels may occur resulting in high calcium levels. (35)

Vitamin C and heart disease:

Carr and Frei recommended a higher vitamin C intake of 90-100 mg per day to avoid chronic diseases. They found prospective studies which demonstrated that a low vitamin C poses a higher risk of cardiovascular disease. (43)

This analysis, was conducted on 19,496 men and women, ages 45 to 79, in the U.K. The participants’ blood was tested for ascorbic acid (a form of vitamin C) and they were placed in five groups (quintiles) according to their serum ascorbic acid levels. Men and women were tracked separately. The researchers observed how many people died of cardiovascular disease, ischemic heart disease, cancer, and all causes in each of the blood ascorbic acid quintiles. In every case (except for women at risk of cancer), death rates were significantly lower among those with higher blood ascorbic acid levels. People with the highest ascorbic acid levels had half the risk of dying from all causes combined. Additionally, a 20 micromol/L increase in blood ascorbic acid concentration, the same as a 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality. (14)

Vitamin C has been shown to be beneficial for people with certain diseases or conditions. High intakes of vitamin C have been associated with decreased risk of heart disease, cancer, eye diseases, and neurological conditions. High dose vitamin C, with an upper tolerable level set at 2 grams per day set by the USDA has been shown to be safe. This limit was set by the USDA due to gastrointestinal side effects. Among healthy individuals, the recommended daily intake of vitamin C is 75 mg for women and 90 mg for men. (15)

Loria and colleagues found an association between low blood ascorbate (vitamin C) levels and an increased risk of dying, overall and from cancer, among men. Compared to men with high ascorbate blood concentraions (73.8 micromol/L or greater), men with low ascorbate blood concentrations (less than 28.4 micromol/L) have a 57% increased total mortality risk and a 62% increased mortality risk from cancer. No change in risk of mortality was found among men with ascorbate blood concentrations between 28.4 to 73.8 micromol/L. No link between mortality and ascorbate levels were found among women. (16)

Calcium supplements may increase mortality:

Calcium and high-dose calcium supplementation was associated with greater cardiovascular (CV) mortality and all-cause mortality in women according to a prospective cohort study of 61,433 women born between 1914 and 1948. Compared with dietary calcium intakes of 600 to 1000 mg daily, daily intakes of ≥1400 mg were associated with significantly higher rates of death from all causes (40% increased risk), CV disease (49% increased risk), and ischemic heart disease (2 times higher risk), but not from stroke. Among the 6% of participant women using calcium supplements (500 mg), those who were also consuming >1,400 mg/d in their diet had a 2.5-times higher risk of all-cause death than women with similar total intakes not taking a supplement. (36)

Calcium supplements increased the risk of cardiovascular events, especially heart attacks, in older women. A re-analysis of data from the Women’s Health Initiative Calcium/Vitamin D Supplementation Study found that among the almost 16,718 women not taking personal supplements at the time of randomization, being randomized to new supplement use (1g calcium and 400 IU vitamin D daily) was associated with a statistically significant increase in risk of cardiovascular events (heart attack, stroke) ranging from 13%-22%. Among women already taking supplements at the start of the study, no such increase in events was seen. A meta-analysis of 3 placebo-controlled trials found that compared to placebo, calcium and vitamin D increased the risk of heart attack by 21%, stroke by 20%, and heart attack or stoke by 16%. (37)

An analysis of 388,229 individuals aged 50 to 71 years found that high calcium intake was associated with an increased risk of cardiovascular disease (CVD) mortality in men, but not women. At study enrollment, 51% of men and 72% of women were taking some form of calcium. The study found that compared to men not taking calcium, men with calcium intake of 1000 mg/day had an elevated risk of total CVD death (20% increased risk) and heart disease death (19% increased risk) but not cerebrovascular disease. In women, there was no association between calcium supplementation and death from cardiovascular disease or cerebrovascular disease. (38)

Vitamin E and omega-3 oil in cardiovascular disease and mortality:

In a randomized controlled trial in Italy published in Lancet, 11,324 patients with pre-existing coronary heart disease (CHD) were randomly allocated to either 300 mg vitamin E, 850 mg omega-3 fatty acid ethyl esters (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), both, or no treatment and followed for 3.5 years. In the end, a 15% reduction in mortality, nonfatal heart attack (myocardial infarction), and nonfatal stroke was seen in participants taking 850 mg omega-3 fatty acid alone. Compared to the no treatment group, participants taking omega-3 fatty acid after 6-months experienced a 2.5% increase in HDL (“good”) cholesterol and a 4% reduction in triglycerides, a type of fat in the bloodstream and fat tissue that can contribute to the hardening and narrowing of arteries. As a group, those taking this dietary supplementation experienced a 20% reduction in all-cause mortality and a 45% reduction in sudden death. The results indicate that in patients who have CHD, omega-3 fatty acid supplements, but not vitamin E, significantly reduced mortality. (17)

Fish oil and mortality:

A review of 14 randomized clinical trials reported that fish oil is associated with a reduction in total mortality and sudden death, but no significant reductions in nonfatal heart attacks were reported. Trials that included supplementation with the plant based alpha-linolenic acid (ALA) showed a possible benefit in reducing sudden death and nonfatal heart attack, but the results were not conclusive. (41)

A 3.5-year study including 11,324 myocardial infarction (MI, heart attack) survivors (MI occurred within 3 months) showed that fish oil supplementation (1 g/day), but not vitamin E (300 mg/day), significantly reduced the total rate of all-cause death, nonfatal MI, and nonfatal stroke. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. (42)

Vegetarian diet in cardiovascular disease and mortality:

A meta-analysis by Huang T et al consisting of 7 studies with a total of 124,706 participants from the UK, Germany, USA, Netherlands and Japan were studied to investigate cardiovascular disease mortality among vegetarians and non-vegetarians. All-cause mortality and mortality from circulatory diseases were lower when compared to non-vegetarians by 9% and 16%, respectively. Researchers also found a significant reduction in the rate of ischemic heart disease mortality by 29% in vegetarians over non-vegetarians. This study suggests vegetarians have a mortality advantage compared to non-vegetarians. (18)

A low carbohydrate, high protein diet and mortality:

A low carbohydrate, high protein diet much like the Atkins style diet, was associated with an increased risk of cardiovascular deaths in women. This is based on a study conducted in Sweden during 1991-1992, and included a 12-year follow-up. It included 42,237 women, ages 30-49. The study associates mortality with varying degrees of increased protein with a stable decreased carbohydrate intake. When the women were noted to decrease carbohydrate intake by 10%, total mortality increased by 6%. When the women were noted to increase protein intake by 10%, total mortality increased by 2%. For those women in the study who were 40-49 years old, the increase in cardiovascular mortality was 13% for those who decreased their carbohydrate intake by 10%. Cardiovascular mortality increased 16% in women that increased their protein intake by 10%. (19)

Tea consumption and heart disease:

Tea consumption appears to result in a reduced risk of heart disease. According to the Ohsaki Study published in the Journal of the Maerican Medical Association, consuming green tea is not only associated with a reduced risk of death from heart disease but also with a reduced risk from all-cause mortality. Researchers followed 40,530 Japanese adults up to 11 years. The results indicated that individuals who consumed the most green tea had lower death rates from cardiovascular disease (CVD) compared to subjects who consumed the least green tea (less than 1 cup/day). Women who drank ≥ 5 cups/day of green tea had a 31% lower risk of dying from CVD and a 23% lower risk of mortality from all causes than women who drank <1 cup/day. Those who drank 1 to 2 cups/day or 3 to 4 cups/day green tea had a 2% and 18% reduced risk of all-cause mortality, respectively. Corresponding risk reductions in CVD were 16% and 31%. The protective effects of green tea was stronger in women than in men. In men who drank ≥ 5 cups/day green tea their all-cause mortality rate fell by 12%. Men who drank 1 to 2 cups/day or 3 to 4 cups/day green tea had a 7% and 5% reduced risk of all cause-mortality, respectively. Green tea consumption was not associated with a reduction in cancer mortality. (20)

Ischemic heart disease (IHD) and a long acting garlic preparation:

A long acting garlic preparation named Allicor reduced the risk of ischemic heart disease (IHD) and sudden death in a year-long study that included 167 participants without IHD and with high levels of lipids/fats in the blood. After 1-year of allicor treatment, the 10-year risk of IHD and acute heart attack plus sudden death were reduced by 10.7% and 22.7%, respectively. A reduction in total cholesterol and LDL ‘bad’ cholesterol for men ( by 27.9 and 22.5 mg/dl, respectively) and women (by 11.4 and 10.8 mg/dl, respectively) was also reported. Cardiovascular risk, related to age, was reduced with use of Allicor in women. (39)

Glucosamine, chondroitin, and mortality:

In one study, glucosamine and chondroitin supplements reduced the risk of total mortality when compared to those who did not take them. Researchers followed 75,510 people aged between 50 and 76 for a period of 5 years. The researchers had information on the subjects’ use of glucosamine and chondroitin, supplements with anti-inflammatory properties, and assessed the effect these supplements had on death. They found that glucosamine and chondroitin use reduced risk of total mortality significantly compared to those who never took these supplements. Specifically, current use of glucosamine was associated with a decreased risk of death (18% and 14% when taken with chondroitin), decreased risk of death from cancer (13%), and decreased risk of death from respiratory diseases (41%). (40)

Coenzyme Q10 levels and survival:

Molyneux and colleagues was the first to formally study the relationship between CoQ10 and outcomes of CHF in a longitudinal observational study which included 236 heart failure patients with a median age of 77 years. Plasma samples were analyzed for CoQ10 and other factors. Over the 5.75 year follow-up period, 39% of the participants who had CoQ10 levels lower than 0.63 micrograms per milliliter died, compared with only 22% of those whose levels were higher. This study also indicated that those with lower CoQ10 were 67% more likely to die. These findings suggested that CoQ10 levels are an independent predictor of survival in chronic heart failure patients. (47)

Reducing risk of mortality in cancer:

Aerobic exercise and cancer:

Alfano et al. completed a study, drawn from the beta-Carotene and Retinol Efficacy Trial, a lung cancer chemoprevention trial, examining physical activity and lung cancer incidence and mortality among 7,045 (59% male) current and former smokers with a mean age of 63 years. Compared to non-active participants, an increase in physical activity resulted in a 14% decreased risk for all-site cancer among men; a 16% decrease risk for lung cancer and a 15% decrease for cancer mortality was seen among younger participants only. Among women, they reported no association between physical activity and lung cancer incidence. Women who were physically active had a 31% decreased risk of lung cancer mortality compared with women who were not physically active. (21)

Aerobic exercise and a low fat, high fiber diet made the blood much less hospitable to prostate cancer cells in vitro. A study authored by Barnard, et al. consisted of using the blood from 3 different groups of 51 to 64 year old males to treat cultured prostate cancer cells in the lab. They compared the blood placed in petri dishes with prostate cancer cells from 3 different groups. The groups included an exercise group that did a consistent exercise program for at least 10 years, a diet plus exercise group who did a consistent diet and exercise program for at least 10 years, and a placebo group. The diet and exercise group were part of a “Pritikin” program and ate low fat, high fiber and complex carbohydrates along with exercise 4-6 days per week. The exercise group exercised for 1 hour per day 5 days per week at a University program in Nevada but did not have any diet program. The placebo subjects were sedentary with poor dietary intake and felt to be at risk of prostate cancer. The blood from the diet plus exercise group caused a significantly greater rate of apoptosis of cancer cells and less growth rate in cancer cells in vitro than the exercise alone or placebo groups. (22)

Serum markers of breast cancer in vivo decreased, and apoptosis in breast cancer cells increased in vitro after diet and exercise. A study involving 38 overweight or obese postmenopausal women adhered to a low-fat (10-15% kcal from fat), high-fiber (30-40 g per 1,000 kcal/d) diet, and participated in a daily exercise class for 2 weeks.  The diet and exercise was found to reduce several serum markers for breast cancer including estrogen, obesity, insulin and insulin-like growth factor-I (IGF-I), even while subjects remained overweight or obese. The in-vitro analysis used serum drawn from the study group before and after the 2 week intervention and placed it with cancer cells. It was found that the growth in different types of breast cancer cell lines was reduced by 6.6-18.5%. Cell death of several different cell types of breast cancer also increased by 20-30% after the intervention. (23)

Beta carotene, vitamins, minerals, omega-3 oils, and cancer:

Antioxidant vitamin supplement, cancer, and all-cause mortality: The SU.VI.MAX Study evaluated 13,017 men and women over a course of 7.5 years randomized to placebo or a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 mcg of selenium, and 20 mg of zinc as a daily dose. These antioxidants were found to result in a lower risk of cancer incidence in men (RR 0.69, 95% CI) and lower risk of all-cause mortality among men (RR 0.63, 95% CI), but not among women participants (RR 1.03 and 1.04 repectively, 95% CI). (45)

Beta-carotene and cancer:

Cancer risk is lower in those who consume beta-carotene containing foods. High blood concentrations of beta-carotene and other carotenoids, plant pigments found in carrots, sweet potatoes, spinach, kale, collard greens, papaya, bell peppers, tomatoes, have been linked to a lower risk of cancer, especially lung, mouth, throat, and cervical cancers. A blood beta-carotene concentration less than 0.28 micromol/L has been linked with a higher risk of several cancers, while a concentration of more than 0.28 to 0.37 micromol/L have been associated with a reduced risk of several cancers in prospective blood concentration studies. However, three other large randomized studies reported no cancer benefit from beta-carotene supplements given at 20, 30, or 50 mg/d for 4 to 12 years. (9)

Beta-carotene supplements are not advised among healthy individuals, unless they suffer from or are at risk of vitamin A deficiency. Beta-carotene supplementation results in a greater increase of beta-carotene blood concentration than beta-carotene rich foods. A 20 mg/d supplement of beta-carotene is associated with blood concentrations high enough to increase a patient’s risk of lung cancer, while the same quantity obtained from foods was not associated with lung cancer risk. Additionally, 30 mg/d of beta-carotene supplement was associated with blood concentrations 5 times greater than that of 29 mg/d of beta-carotene from carrots. The consumption of 5 or more daily servings of fruits and vegetables is recommended by “National Cancer Institute’s Five-A-Day for a Better Health program” and “Canada’s Food Guide for Healthy Eating.” Eating a variety of 5 fruits and vegetables per day provides the individual with about 5.2 to 6 mg/day of food based beta-carotene. This allows plasma carotenoid levels to rise above a range represented in studies which were associated with a lower risk of cancer and all-cause mortality compared to those with a lower food based carotenoid levels. (9)

Intake of vegetables containing beta carotene was associated with a lower risk for all causes of death including cancer but no benefit was seen with taking beta-carotene supplements. Greenberg ER et al tested beta carotene levels in subjects prior to being randomized to take beta carotene supplements. Subjects with an intial beta carotene level of 0.34 to 0.52 umol/L had a 51% less risk of dying from cancer when compared to subjects with the lowest intial beta carotene levels of under 0.21 umol/L. Those subjects with an intitial beta carotene level of over 0.52 umol/L had a lower risk of death from all causes. There was no reduced risk of disease or mortality benefit in subjects who took beta carotene supplements in pill form (8).

The Beta-Carotene and Retinol Efficacy Trial (CARET), showed that among 18,314 men and women who smoked heavily or were exposed to asbestos, daily intake of 30 mg (100,000 IU) of beta-carotene and 25,000 IU vitamin A failed to decrease the risk of cancer. The study was stopped early because it showed that beta-carotene/vitamin A takers who were heavy smokers, ex-smokers or asbestos workers were showing a 28% increased risk of lung cancer in smokers (versus placebo) and a 17% more likely chance of dying, mostly of lung cancer or heart disease.  Results of a 6-year follow-up of study participants showed that compared to the placebo or no intervention group, participants who had taken the intervention had a 12% and 8% increase in relative risk of lung cancer and all-cause mortality among the intervention group, respectively. They found that women were more affected by the supplements with a larger relative risk of lung cancer mortality (1.33 versus 1.14; P = .36), and all-cause mortality (1.37 versus 0.98; P = .001) than males. (10)

According to Martini et al in the University of Minnesota Cancer Prevention Research Unit Feeding Studies, an intake of 5 mg per day of beta carotene was required to establish beta carotene levels to a plasma level of 0.37 micromol/L. When food based beta carotene was consumed in the form of about 1.5 cups of carrots, and about 0.9 cups of spinach which equated to just over 42 mg of beta-carotene per day, levels increased to 0.83 micromol/L. (11)

For a breakdown of concentration of beta-carotene in foods, please see: Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. This may be accessed at: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w321.pdf and http://www.nal.usda.gov/fnic/foodcomp/Data/HG72/hg72_2002.pdf

A meta-analysis that included 78 randomized clinical trials was conducted to determine the relationship of oral antioxidant supplementation (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) and mortality. Mean duration of supplementation was 3 years. When all of the trials were combined, and the analysis that is typically used when similarity is present was conducted (fixed-effect model), antioxidant use did slightly increase mortality. When the trials with low risks of bias were considered, the patients consuming the antioxidants had a 4% higher risk of death compared to those taking placebo or no intervention (relative risk [RR]=1.04). The increased risk of mortality was significantly associated with use of beta-carotene (death rate: 13.8% on supplement vs 11.1% on placebo; RR=1.05) and vitamin E (12.0% vs 10.3%; RR=1.03) and possibly vitamin A, though the relationship was not significant with a 14.0% death rate among those taking vitamin A compared to a 13.6% death rate among placebo subjects. The current evidence does not support the use of these antioxidant supplements in the general population or in patients with various diseases. (12)

The studies mentioned thus far on beta-carotene suggest a lower risk of mortality stems from beta carotene intake from food sources but not beta-carotene supplements. The benefit may also come from other substances in the vegetable food source and not necessarily the beta carotene itself.

Calcium and cancer:

Calcium together with vitamin D supplements have been linked with a decrease in the relative risk of various cancers in women excluding skin cancers. A population-based randomized 4-year study conducted in Nebraska enrolled 1179 women aged 55 years and older, with no known cancer. Participants were randomly assigned to 3 groups: 1) Placebo (calcium placebo plus vitamin D placebo, n=266); 2) calcium-only (1400 mg calcium citrate or 1500 mg calcium carbonate plus vitamin D placebo, n=416); and Calcium + D (1000 IU [25 mcg] vitamin D plus calcium [as above], n=403). Serum samples were analyzed for levels of 25(OH)D, vitamin D, at baseline and then yearly. Study results found 50 women developed non-skin cancer during the study: 13 in the first year, and 37 during the second to fourth years. The relative risk reduction (RRR) for the calcium + D group was 0.232 (confidence interval [CI], 0.09–0.60; P<.005), and the RRR for the calcium-only group was 0.587 (95% CI, 0.29–1.21; P=.147) compared with the placebo group. Increasing the dose of vitamin D from the current standard of 400–600 IU per day to 1000 IU per day may lower future risk of cancer in women older than age 55 who do not get adequate vitamin D from sun exposure or diet. The conclusion of the author was that an improvement of nutritional status with calcium and vitamin D significantly lowers cancer risk. (31)

Calcium intake may reduce the risk of colon cancer. In a meta-analysis by Carroll C. et al, 3 trials showed a reduction of recurrence of colon adenomas for subjects who took 1200 – 2000 mg per day of a calcium supplement, but no decrease in risk for those with advanced adenomas. Also as part of the meta-analysis, 2 trials were found to have no benefit of calcium in those without increased risk of colorectal cancer. (32)

Excess calcium intake appears to increase the risk of prostate cancer in men.

A study which evaluated a cohort of over 65,000 men over a period of 6-7 years revealed that intake of calcium over 2000 mg per day in the form of dietary and supplement intake was associated with a moderate increase in risk of prostate cancer. The risk of prostate cancer was not increased with dairy intake. There was also no increase in risk of prostate cancer with moderate or low levels of dietary calcium intake. (33)

Chung et al reviewed calcium and prostate cancer risk as part of a systematic review of health outcomes. He found that a number of studies reported that high calcium intakes were associated with an increased risk of prostate cancer. (34)

Calcium and breast cancer:

Chung, et al reviewed a number of studies on health outcomes by subjects which consumed calcium and vitamin D. It was found that adequate calcium intakes in premenopausal women was associated with a decreased risk of breast cancer. (34)

Vitamin D and cancer:

Investigators followed a total of 1,194 men over a median duration of 12.7 years in a longitudinal study looking at the link between blood levels of vitamin D and mortality. They looked at vitamin D levels and cancer-related as well as all-cause mortality. There was a clear U-shaped curve when looking at the relationship between vitamin D levels and all-cause mortality along with cancer-related mortality, meaning the risk of mortality was significantly increased at both low and high blood levels of vitamin D. In this study, the range with the lowest mortality was about a vitamin D concentration of 24 to 34 ng/ml (60 to 85 nMol/L), which approximately translates to a vitamin D dose of 2000 IU/d. In general, the biggest drop in overall death rates were seen when subjects went from being vitamin D deficient to reaching adequate levels. However, too much vitamin D translated into a gradual increase of mortality rate with cancer deaths rising significantly for the highest levels of vitamin D intake. Overall mortality was increased by 50–60% among subjects in the lowest 10% and highest 5% of the vitamin D distribution. The ideal vitamin D dose according to findings in this study is 2000 IU/d. (13)

Vitamin D is important for reducing the risk of various cancers, A report by the Institute of Medicine (IOM) and the Endocrine Society’s Clinical Practice Guidelines tripled the amount of vitamin D required for most children and adults. The Endocrine Society’s Clinical Guidelines for vitamin D concluded that vitamin D deficiency be defined as a 25(OH)D < 20 ng/ml, insufficiency as a 25(OH)D of 21–29 ng/ml and sufficiency as a 25(OH)D of 30–100 ng/ml. For preventing and treating vitamin D deficiency the Guidelines recommended vitamin D intake should be: children < 1 y 400-1,000 IU/d, children 1-18 y 600-1,000 IU/d and adults 1,500-2,000 IU/d to maintain 25(OH)D concentrations of 40–60 ng/ml.  Upper limits of vitamin D intake were also set as follows: 2000 IU/day for children up to age 1 year; 4000 IU/day for children aged 1 – 18 years, and up to 10,000 IU/day for adults aged 19 years and older. The IOM report concluded that dietary and supplemental vitamin D intake is adequate to satisfy both children and adult, but their study suffered from serious flaws. A study (Moore et al) suggests that neither children nor adults in the US are obtaining the new RDA for vitamin D. Among women vitamin D intake from food was 156–208 IU/d and with supplements 244–324 IU/d. For men, corresponding values were 208–320 IU/d and 308–392 IU/d. There is no evidence that there is a downside to increasing vitamin D intake in children and adults, with the exception of those with chronic granuloma forming disorder or lymphoma in which high vitamin D levels may occur resulting in high calcium levels. (35)

Vitamin C and cancer:

Loria and colleagues found an association between low blood ascorbate (vitamin C) levels and an increased risk of dying overall and from cancer, among men. Compared to men with high ascorbate blood concentraions (73.8 micromol/L or greater), men with low ascorbate blood concentrations (less than 28.4 micromol/L) have a 57% increased total mortality risk and a 62% increased mortality risk from cancer. No change in risk of mortality was found among men with ascorbate blood concentrations between 28.4 to 73.8 micromol/L. The vitamin C intake corresponding to the higher risk of mortality in men was less than or equal to 60 mg per day. No link between mortality and ascorbate levels were found among women. (16)

Carr and Frei recommended a higher vitamin C intake of 90-100 mg per day to avoid chronic diseases and showed somewhat different findings after reviewing cohort studies. They found that low intake of vitamin C was related to an increase in cancer mortality. They also had a different conclusion than Loria et al in that intake of vitamin C was inversely related to cancer mortality in elderly women but not mortality in men. (43)

An analysis, was conducted on 19,496 men and women, ages 45 to 79, in the U.K. The participants’ blood was tested for ascorbic acid (a form of vitamin C) and they were placed in five groups (quintiles) according to their serum ascorbic acid levels. Men and women were tracked separately. The researchers observed deaths from cancer and all causes in each of the blood ascorbic acid quintiles. In every case (except for women at risk of cancer), death rates were significantly lower among those with higher blood ascorbic acid levels. People with the highest ascorbic acid levels had half the risk of dying from all causes combined. Additionally, a 20 micromol/L increase in blood ascorbic acid concentration, the same as a 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality. (14)

Vitamin C has been shown to be beneficial for people with certain diseases or conditions. High intakes of vitamin C have been associated with decreased risk of heart disease, cancer, eye diseases, and neurological conditions. High dose vitamin C, with an upper tolerable level set at 2 grams per day set by the USDA has been shown to be safe. This limit was set by the USDA due to gastrointestinal side effects. Among healthy individuals, the recommended daily intake of vitamin C is 75 mg for women and 90 mg for men. (15)

Nutrition, foods and diet related to cancer:

A meta-analysis by Huang T et al consisting of 7 studies with a total of 124,706 participants from the UK, Germany, USA, Netherlands and Japan investigated cancer incidence among vegetarians and non-vegetarians. All-cause mortality in vegetarians was found to be lower when compared to non-vegetarians. Researchers also found a statistically reduced rate for vegetarians in terms of cancer incidence of 18%. This study suggests vegetarians have a mortality advantage compared to non-vegetarians. (18)

A study by McCann SE et al evaluated the association between dietary lignin intake and survival. Lignans are antioxidants and phytoestrogens (chemicals that can act like hormone estrogen) found in a variety of plants, which includes flax seeds, pumpkin seeds, rye, soybeans, broccoli and some berries. However, flax seed have the highest amount of lignans available from common nutritional sources. The data used in this study came from 1,122 women diagnosed with breast cancer between 1996 and 2001. Diet in the 12-24 months before diagnosis was assessed. For the women enrolled in this study, the main food sources of lignans were dark bread, peaches, coffee, broccoli and winter squash. Researchers estimated the average lignan intake among the women to be 244 mcg/day. They also found a 51% reduction in all cause mortality in those consuming higher lignan levels (the lowest risk of dying was seen in women consuming >318 mcg per day). These same women were far less likely to die of breast cancer. They had a 71% decreased risk of dying of breast cancer. The intake of dried beans was also associated with a 39% reduced risk of all-cause mortality. (24)

Aspirin use for the prevention of cancer:

In a study by Bardia A et al, regular aspirin use was associated with a lower cancer incidence and cancer mortality, but non-aspirin non-steroidal anti-inflammatory drug (NSAID) use was not. The beneficial effects of aspirin were stronger in former and never smokers than current smokers. Among 22,507 cancer-free postmenopausal women age 55-69 who provided information on aspirin and NSAID use, those who said they regularly used aspirin had a 16% reduced risk of developing cancer more than a decade later. There was also a 13% reduced risk of dying from cancer over this same time period, compared to women who did not use aspirin. Aspirin use decreased the risk of mortality from coronary artery disease by 25% and reduced the risk of all-cause mortality by 18%. Ever use of aspirin was associated with a lower risk of cancer than those women who never used aspirin. Aspirin use greater than 6 times per week was compared to aspirin use 2-5 times per week, over 1 time per week, ever use , and never use. The higher the frequency of aspirin use, the lower the incidence of cancer. Also the higher the frequency of aspirin use, the lower the cancer mortality. The women with the lowest all-cause mortality took aspirin 2-5 times per week. There was no statistically significant impact on cancer incidence or mortality among women who used non-aspirin NSAIDs, compared to those who did not. (29)

To prevent colorectal cancer in individuals at average risk for colorectal cancer the U.S. Preventive Services Task Force (USPSTF) recommends against the routing use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). According to the USPSTF, aspirin is required in higher doses than cardiovascular and ischemic stroke prevention. The higher doses of aspirin and NSAIDs required to prevent polyps and colorectal cancer poses a risk of severe bleeding episodes. Therefore, the USPSTF has determined that the risk of hemorrhagic stroke with aspirin outweighs the benefit of colorectal cancer prevention. The risk of gastrointestinal bleeding and hemorrhage with NSAIDs outweigh the benefits of colorectal cancer prevention. (30)

The USPSTF recommends against aspirin for prevention of colorectal cancer because it requires higher doses in order to accomplish this, but if aspirin is recommended for cardiovascular disease or stroke prevention, there would still be benefit obtained in the prevention of cancer, since according to the study by Bardia A et al, cancer incidence and cancer mortality was reduced even in patients that used aspirin infrequently compared to those that never used it (29).

Red wine and esophageal, gastric cancer risk:

Gammon et al performed a population-based case-control study on 1,143 patients with esophageal and gastric adenocarcinoma and compared them to controls to determine the risk factors of these cancers. The authors found that esophageal and gastric cancer odds ratio was 0.6 with a 95% confidence interval in drinkers of wine which translated to 40% lower odds of these cancers occurring in wine drinkers over controls. Beer drinkers and liquor drinkers were not found to be associated with esophageal and gastric cancer. Of note, smoking significantly contributed to esophageal and gastric adenocarcinoma and was believed by the authors to cause about 40% of these cancers (44)

Colorectal cancer screening:

The U.S. Preventive Services Task Force (USPSTF) recommends screening for colorectal cancer for all individuals 50 – 75 years old with either fecal occult blood testing every year, fecal occult blood testing every 3 years plus sigmoidoscopy every 5 years, or screening colonoscopy every 10 years, all of which will reduce mortality of the population (45). See our colorectal cancer section for further information.

Reducing risk of stroke related mortality:

Women and aspirin for a lower mortality: Cardiovascular events were not reduced in women by aspirin and therefore they are not believed to benefit from aspirin for heart disease but they do benefit from aspirin in the prevention of ischemic stroke (45).

Prevention of ischemic stroke in women:

According to the U. S. Preventive services Task Force (USPSTF),women benefit from aspirin for the prevention of ischemic stroke (45).

Women age 55 to 79 years: The USPSTF strongly recommends aspirin when the potential benefit due to a reduction in ischemic strokes (which occur when an artery to the brain is blocked) is more beneficial than the potential harm due greater gastrointestinal hemorrhage.

Women 55 years old or younger: The USPSTF recommends against the use of aspirin for stroke prevention since the benefit for prevention of ischemic stroke is small.

A calculator for the risk of stroke is available here (2): http://www.westernstroke.org/PersonalStrokeRisk1.xls  Western States Stroke Consortium, Neurocritical Care and Stroke Division, University of Southern California, 1100 N. State St., Clinic Tower A4E111, Los Angeles, CA 90033, Tel: 323-409-7381    Fax: 323-441-8093 Link is also available at: Aspirin for the Prevention of Cardiovascular Disease, Topic Page. December 2009. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsasmi.htm

Wine consumption and stroke mortality:

Stroke mortality was reduced with low to moderate intake of wine. A study done in Copenhagen, Denmark followed 6051 men and 7234 women between 30 and 70 years old. The relative risk of cerebrovascular mortality (stroke mortality) was significantly less for those who had a low to moderate intake of wine. It was found that beer intake did not change mortality risk much and that drinking spirits increased mortality. (6)

Mortality in vegetarians vs. non-vegetarians:

A meta-analysis by Huang T et al consisting of 7 studies with a total of 124,706 participants from the UK, Germany, USA, Netherlands and Japan was conducted to investigate mortality among vegetarians and non-vegetarians. All-cause mortality and mortality from cerebrovascular diseases in vegetarians were lower when compared to non-vegetarians by 9% and 12%, respectively. This study suggested vegetarians have a mortality advantage compared to non-vegetarians. (18)

Mortality due to respiratory causes may be reduced by a mineral:

Mortality due to respiratory causes appears to be reduced with a mineral supplement used by patients with age-related macular degeneration (AMD), an aging change in the back of the eye that may lead to loss of the central vision. The study reported the beneficial effect of antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; beta carotene, 15 mg; and zinc, 80 mg as zinc oxide with 2 mg of cupric oxide) on the risk of AMD progression among Age-Related Eye Disease Study (AREDS) participants. Investigators also examined the relationship between AMD, cataract and mortality. During a median follow-up of 6.5 years, 11% or 534 participants had died. This marked an increased mortality risk among participants with advanced AMD. However, participants randomly assigned to receive 80 mg zinc with 2 mg cupric oxide(high does zinc is associated with copper deficiency), whether alone or combined with antioxidants, had lower mortality than those not taking the mineral. They report a 27% lower relative risk of mortality for zinc alone, and a 12% lower relative risk for those who took zinc combined with beta-carotene, vitamin C and vitamin E. The beneficial effect of zinc on mortality was associated with less death from respiratory causes. (25)

Mortality related to inflammatory disease:

Gopinath Bet al researched data on 2,514 subjects aged 49 years of age or older at baseline, out of which 214 died of inflammatory diseases including infection, hematological, immunologic, endocrine, nutritional, metabolic, nervous system, respiratory, digestive system, musculoskeletal, connective tissue, skin, and genitourinary diseases over the course of 15 years. Daily intake of oils in the diet were analyzed and few of the subjects took any oil supplements. Special questionaires were used to determine intakes of omega-3 oils from fats, oils, fish, seafood, meat, bread, cereals, and milk products. Compared to women with the lowest third of omega-3 fat intake (0 to 740 mg per day), women with the highest third of omega-3 fat intake (1.1 – 4.72 grams per day) had a 44% reduced risk of mortality from inflammatory diseases.  Even the middle third of omega-3 intake (750 – 1000 mg per day) showed a 39% decreased risk (P = 0.03).  This same connection was not found in men. Regarding nut consumption, both men and women showed reduced risks of inflammatory disease, with a 40% reduction risk for the highest third of nut intake (4.9 – 100 grams per day) and a 54% reduced risk for the middle third of nut intake (1.4 – 4.55 grams per day).  In conclusion, including omega-3 fatty acids and nuts in the diet can significantly decrease the risk of mortality from inflammatory disease. (26)

Other possibilities for lifespan and longevity enhancement:

Aerobic fitness and brain volume: Aerobic fitness maintains brain volume and cognitive function. Previous research has demonstrated that the human brain gradually loses tissue density after the age of thirty in the frontal, parietal, and temporal cortices as a function of the aging process.  In this study, MRIs of people 55 years and older showed that there were marked differences in brain tissue densities based upon age and amount of aerobic fitness.  The study showed that people involved in cardiovascular fitness greatly maintained more brain volumes and cognitive function in these areas of the brain. (27)

Polyphenols and lifespan: Based on a study provided by the Division of Dermatology, University of Kansas, individuals with dietary restrictions combined with antioxidants containing polyphenols actually extends lifespan. Polyphenols are an organic chemical present in plants with antioxidant action. In the study mice were placed on one of three diets. These included a diet of continuous feed; alternate day eating; and alternate day eating supplemented with polyphenol antioxidants including blueberry, pomegranate and green tea extracts. The supplemented group outlived the other two groups. (28)

Pomegranate May Provide Incredible Anti-aging Benefits

New research suggests that pomegranate may provide incredible anti-aging benefits to boost longevity. Recent research at the Laboratory of Integrative Systems Physiology in EPFL, Lausanne, Switzerland has demonstrated extension of lifespan in animals. It is believed that pomegranate provides an anti-aging effect different then any other mechanism previously discovered. When polyphenols in pomegranate were consumed, it was changed by certain bacteria in the stomach into a compound called urolithin A.

How Pomegranate May Boost Longevity

The compound urolithin A was able to enhance longevity by maintaining healthy mitochondria and extend life span in worms by 50%. It was also found to significantly extend exercise endurance in mice by 40%. Over time, mitochondria develop alterations that cause them to degrade. Urolithin A derived from pomegranate is believed to keep mitochondria healthy by inducing a process called mitophagy.

Pomegranate May Induce Mitophagy

Mitophagy is the process that maintains healthy mitochondria in the cell. Mitophagy is believed to enhance lifespan and longevity by keeping cells healthy and there is hope that these benefits provided by urolithin A will translate to humans. It is possible in the future that pomegranate anti-aging benefits may boost longevity by 50%, and may be used to treat chronic diseases as well as extend lifespan.

Summary: Anti-aging, Increasing Lifespan, and Reducing Risk of Mortality

• The American Heart Association proposed metrics to reduce risk the risk of cardiovascular mortality over the next 11 years by 50-60% compared to patients that meet only 2 out of 8 or fewer criteria. In order to do this, make goals to meet at least 3 out of 4 of the following (1):

1) total cholesterol lower than 200 mg/dL

2) blood pressure lower than 120/80 mm Hg

3) not having diabetes

4) free of heart disease

AND meet at least 2 out of 4 of the following:

1) no smoking

2) normal body mass index (BMI)

3) engaging in physical activity

4) eating healthfully

• U.S. Preventive Services Task Force (USPSTF) recommendations for the use of aspirin in prevention of cardiovascular disease (45):

• Aspirin dosage: According to the USPTF, the ideal dose of aspirin is not known, but a dose of 75 mg per day appears as effective as higher doses and may have less risk of gastrointestinal bleeding.

• Men benefit from aspirin for the prevention of cardiovascular disease.

• Men younger than 45 years: For myocardial infarction prevention in men younger than 45 years the USPSTF recommends against the use of aspirin since the benefit for prevention of cardiovascular events are small.

• Men age 45 to 79 years: The U.S. Preventive Services Task Force (USPSTF), strongly recommends the use of aspirin when the potential benefit due to a reduction in myocardial infarctions is more beneficial than the potential harm due to gastrointestinal hemorrhage.

• Men and Women 80 years of age and older: According to the U.S. Preventive Services Task Force (USPSTF), there is insufficient evidence to determine the risk verses benefit of taking aspirin by men and women over 79 years of age for the prevention of cardiovascular disease.

• If considering the use of aspirin for the prevention of cardiovascular disease or ischemic stroke, an additional benefit of reduced risk of colon cancer is possible but this reduced risk is usually associated with higher doses of aspirin which are unsafe (45) .

• According to the U. S. Preventive services Task Force (USPSTF),women benefit from aspirin for the prevention of ischemic stroke (45):

• Women age 55 to 79 years: The USPSTF strongly recommends aspirin when the potential benefit due to a reduction in ischemic strokes (which occur when an artery to the brain is blocked) is more beneficial than the potential harm due greater gastrointestinal hemorrhage.

• Women 55 years old or younger: The USPSTF recommends against the use of aspirin for stroke prevention since the benefit for prevention of ischemic stroke is small.

• A calculator for the risk of stroke is available here and on the USPSTF website (2,45): http://www.westernstroke.org/PersonalStrokeRisk1.xls   Western States Stroke Consortium, Neurocritical Care and Stroke Division, University of Southern California, 1100 N. State St., Clinic Tower A4E111, Los Angeles, CA 90033, Tel: 323-409-7381    Fax: 323-441-8093 Link is also available at: Aspirin for the Prevention of Cardiovascular Disease, Topic Page. December 2009. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsasmi.htm

• Continue or begin an aerobic exercise program which may reduce overall mortality. For the beginner, please see the aerobic exercise section.

• Low to moderate alcohol intake reduces risk of cardiovascular mortality. Physicians are reluctant to recommend alcohol intake even for health reasons. Prior to considering alcohol use daily or several times per week, discuss the risks and health benefits with the primary physician. Research supports a benefit somewhere in the range between 1-4 alcohol drinks per day for men and 1-2 drinks per day for women. 1 drink is defined as 1.5 ounces of 80-proof liquor, 5 ounces of wine or 1 can of beer. Consider drinking only red wine which has a greater benefit seen in research over all other types of alcohol beverages. Alcohol taken for health reasons may reduce the risk of myocardial infarction, ischemic stroke, dementia associated with stroke, Alzheimer\’s disease, and may improve the cholesterol profile. For more information, please see the alcohol and red wine sections.

• Gammon et al found that red wine can reduce the risk of some gastrointestinal cancers and that smoking will significantly increase this risk. Drinking red wine was associated with a lower risk of esophageal and gastric cancer with an odds ratio of 0.6 with a 95% confidence interval. This translated to 40% lower odds of these cancers occurring in wine drinkers over controls. Beer drinkers and liquor drinkers were not found to have an association with esophageal and gastric cancer. Of note, smoking significantly contributed to esophageal and gastric adenocarcinoma and was believed by the authors to cause about 40% of these cancers. (44)

• A long acting garlic preparation named Allicor reduced the risk of ischemic heart disease (IHD) and sudden death in a year-long study that included 167 participants without IHD and with high levels of lipids/fats in the blood.

• The SU.VI.MAX Study evaluated 13,017 men and women over a course of 7.5 years randomized to placebo or a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 mcg of selenium, and 20 mg of zinc as a daily dose were found to result in a lower risk of cancer and all-cause mortality among men but not among women. (45)

• Beta carotene intake in the form of vegetables was associated with a lower risk of cardiovascular and cancer mortality and with a lower risk for death from all causes. Do not consume beta-carotene supplements as no benefit was seen and these may be harmful. Eating 5 fruits and vegetables per day provides the individual with about 5.2 to 6 mg/day of food based beta-carotene. This amount allows plasma carotenoid levels to rise to a plasma level of 0.37 umol/L associated with a lower risk of cancer, cardiovascular and all-cause mortality. A beta-carotene level of 0.34 to 0.52 umol/L is ideal. When food based beta carotene was consumed in amounts over 42 mg per day, levels increased to 0.83 umol/L which is higher than necessary. To see concentrations of beta-carotene in foods, please see: Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. This may be accessed at: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w321.pdf and http://www.nal.usda.gov/fnic/foodcomp/Data/HG72/hg72_2002.pdf

• The conclusion of a study by Lappe JM stated that an improvement of nutritional status with calcium and vitamin D significantly lowers cancer risk.

• At this time, after acknowledging the release of new data from cohort studies, it is advisable for men and women to avoid a total daily calcium intake of over 1400 mg per day from diet and supplements due to an increased risk of cardiovascular mortality. Calcium supplements are not advised and risk may outweigh the benefit if the amount of calcium taken in the diet is unknown, or exceeds 1000 mg per day until further research clarifies these findings.

• In a meta-analysis by Carroll C. et al, 3 trials showed a reduction of recurrence of colon adenomas for subjects who took 1200 – 2000 mg per day of a calcium supplement, but no decrease in risk for those with advanced adenomas.

• Intake of calcium over 2000 mg per day by men in the form of dietary and supplement intake was associated with a moderate increase in risk of prostate cancer.

• Adequate calcium intake in premenopausal women appears to be associated with a decreased risk of breast cancer.

• The USPSTF recommends screening for colorectal cancer for all individuals 50 – 75 years old with either fecal occult blood testing every year, fecal occult blood testing every 3 years plus sigmoidoscopy every 5 years, or screening colonoscopy every 10 years, all of which will reduce mortality of the population (45).

• The vitamin D3 ideal dose for adults appears to be 2000 international units (IU) per day which reduced cardiovascular mortality, cancer mortality and all-cause mortality. The 2000 IU dose established a vitamin D level about 24 to 34 ng/ml (60 to 85 nMol/L) resulting in the lowest mortality. The biggest drop in overall death rates were seen when subjects went from being vitamin D deficient to reaching adequate levels. Also, excess intake of vitamin D translated into a gradual increase of mortality rate. For a general picture, overall mortality was increased by 50–60% among subjects in the lowest 10% and highest 5% of the vitamin D level distribution.

• The Institute of Medicine (IOM) and the Endocrine Society’s Clinical Practice Guidelines defined vitamin D deficiency as a 25(OH)D < 20 ng/ml, insufficiency as a 25(OH)D of 21–29 ng/ml and sufficiency as a 25(OH)D of 30–100 ng/ml (35) :

• For preventing and treating vitamin D deficiency the Guidelines recommended vitamin D intake should be the following to maintain 25(OH)D concentrations of 40–60 ng/ml:

• children < 1 y 400-1,000 IU/d

• children 1-18 y 600-1,000 IU/d

• adults 1,500-2,000 IU/d

• Upper limits of vitamin D intake were also set as follows:

• 2000 IU/day for children up to age 1 year

• 4000 IU/day for children aged 1 – 18 years

• up to 10,000 IU/day for adults aged 19 years and older.

• For more information, see the section on vitamin D. Vitamin D is also important in other ages and for more information see section on vitamin D.

• Maintain adequate vitamin C intake. Among healthy individuals, the recommended daily intake of vitamin C is 75 mg for women and 90 mg for men to maintain plasma levels over 28.4 micromol/L. High dose vitamin C with an upper tolerable level set at 2 grams per day has been shown to be safe according to the USDA and set at this dose due to gastrointestinal side effects but benefit of this high dose shows mixed results in studies. Vitamin C is also important in other ages and for more information see section on vitamin C.

• Carr and Frei recommended a higher vitamin C intake of 90-100 mg per day to avoid chronic diseases. They found that low intake of vitamin C was related to an increase in cancer mortality. Vitamin C was inversely related to cancer mortality in elderly women but not in men. Loria et al found a similar conclusion of an increase in cancer mortality among men but not women with low vitamin C levels. Loria found that the vitamin C intake corresponding to the higher risk of mortality in men was less than or equal to 60 mg per day.

• Women who drank ≥ 5 cups/day of green tea had a 31% lower risk of dying from cardiovascular disease (CVD) and a 23% lower risk of mortality from all causes than women who drank <1 cup/day. Those who drank 1 to 2 cups/day or 3 to 4 cups/day green tea had a 2% and 18% reduced risk of all-cause mortality, respectively. Corresponding risk reductions in CVD were 16% and 31%. The protective effects of green tea was stronger in women than in men. In men who drank ≥ 5 cups/day green tea their all-cause mortality rate fell by 12%. Men who drank 1 to 2 cups/day or 3 to 4 cups/day green tea had a 7% and 5% reduced risk of all cause-mortality, respectively. Green tea consumption was not associated with a reduction in cancer mortality.

• In one study, glucosamine and chondroitin supplements reduced the risk of total mortality when compared to those who did not take these.

• Patients on a vegetarian diet compared to non-vegetarians had a reduced all-cause mortality by 9%, reduced mortality from circulatory diseases by 16%, reduced rate of ischemic heart disease mortality by 29%, and lower cancer incidence of 18%.

• For any previous diagnosis of age-related macular degeneration, consider taking 80 mg zinc with 2 mg cupric oxide to reduce mortality associated with respiratory causes.

• Include foods with omega-3 oils and nuts in the daily diet for reduced mortality found in inflammatory diseases. Compared to women with the lowest third of omega-3 fat intake (up to 740 mg per day), women with the highest third of omega-3 fat intake (1.1 – 4.7 grams per day) had a 44% reduced risk of mortality from inflammatory diseases. Both men and women showed reduced risks of inflammatory disease mortality with a 40% reduction risk for the highest third of nut intake (4.9 – 100 grams per day) and a 54% reduced risk for the middle third of nut intake (1.4 – 4.55 grams per day). Fish intake, long chain polyunsaturated oils and omega-6 oils did not affect mortality.

• A review of 14 randomized clinical trials reported that fish oil is associated with a reduction in total mortality and sudden death, but no significant reductions in nonfatal heart attacks were reported. An additional study showed that fish oil at a dose of 1 gram per day significantly reduced the total rate of all-cause death, nonfatal MI, and nonfatal stroke. Please see the section on fish oil for additional information including adverse reactions and interactions of fish oil/ omega 3 fatty acids.

• The polyphenols blueberry, pomegranate and green tea may help protect against Alzheimer\’s disease, but no specific data is available regarding relationship to mortality (however, protecting one\’s self from Alzheimer\’s disease may in turn, reduce chances of mortality due to this disease).

• In at least one study, green tea decreased risk of cardiovascular disease and all-cause mortality especially for drinking 4 or more cups per day but data interpretation in the research showed that women had a greater mortality benefit than men.

• Molyneux, SL et al studied 236 heart failure patients at the average age of 77 for 5.75 years and found that 39% with coenzyme Q10 levels under 0.63 mcg per ml died, compared with only 22% of subjects with higher levels translating to a 67% higher risk of mortality and the author believed coenzyme Q10 levels were an independent predictor of survival (47).

• Research suggests that pomegranate may provide anti-aging benefits to boost longevity (48)

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