~Fasting and Calorie Restriction, Part 3 - CRON, continued

~Fasting and Calorie Restriction, Part 3 - CRON, continued
Calorie Restriction and the Heart

According to Dr. Tomas Prolla (professor of genetics, University of Wisconsin), "It appears that if people reduce their current caloric intake between 20 and 40% -- even starting in middle age -- they may delay the development of heart disease or possibly even prevent it." Dr. Barbara Hansen, director of the Obesity and Diabetes Research Center at Johns Hopkins University in Baltimore Md., agreed that animals whose food intake was reduced by about one-third developed less heart disease later in life than animals allowed to eat at will. The hearts of mice on a low-calorie diet showed nearly 20% fewer age-related genetic changes and also appeared to have less DNA damage than those of mice on regular diets (Parker 2002).

Recall the persuasive cardiovascular results obtained from the Biosphere II experiment. In the first 6 months, body weight dropped an average of 15%, blood sugar dropped 20%, blood cholesterol dropped 38% and blood pressure dropped significantly (30% systolic and 27% diastolic) on a calorie restricted diet (Walford 1994; Best 1995).

In addition, a 30% reduction in caloric intake in 30 rhesus monkeys (over a 6 to 7 year time frame) led to up to a 25-point elevation in HDL2B and up to a 20-point decrease in triglycerides. Increases in HDL2B and decreases in triglycerides of this magnitude in humans would be a great health benefit, especially for those at risk for stroke or heart disease (Verdery et al. 1997; Lane et al. 1999). Lastly, multiple studies have shown an increase in insulin sensitivity (up to 4 times greater) and a decrease in insulin levels when practicing calorie restriction (Spindler 2001b) (hyperinsulinemia appears a forerunner of many of the risk factors associated with heart disease).

Convincing Summation

According to the Harvard Medical School, calorie restriction has been shown to increase longevity in organisms ranging from yeast to mammals (Bluher et al. 2003). Researchers at the University of Texas Health Science Center (San Antonio) explain that the remarkable effects of restricting food intake to 50 to 70% of that eaten by ad lib-fed rodents appears to occur through three biological mechanisms: (1) reduction in oxidative damage; (2) modulation of glycemia and insulinemia; and (3) hormesis (a beneficial biological action from a factor or agent that is generally perceived as detrimental; life span extension by dietary restriction is an example of hormesis) (Masoro 1998, 2000).

Unfortunately, at least a 30% reduction in calories appears necessary to realize a significant health advantage from dietary restrictions. According to Richard Miller, associate director for research at the University of Michigan Geriatrics Center, such austerity requires a psychological profile that only one person in 1,000 possesses. Thus, according to Miller, "The best objective may not be to develop another diet that people will not follow but rather to concoct a pill or potion that mimics the beneficial effects of calorie restriction" (Taubes 2000). For example, a new agent, which mimics the function of a compound called PPAR-delta, seems to provide similar benefits to calorie restriction (at least in monkeys).

Middle-aged, insulin resistant, male monkeys (displaying imbalances in blood lipids) were administered the PPAR mimic (PPAR-delta is involved in the regulation of fat transport and insulin sensitivity). After 4 weeks on the PPAR imitator, the monkeys had HDL cholesterol levels 79% higher, triglyceride concentrations 56% lower, and increased insulin sensitivity. It is unknown whether the PPAR-delta mimic would lengthen life span in humans by addressing insulin sensitivity and blood cholesterol levels in people who do not appear to be at risk of developing either diabetes or heart disease. Before these questions can be answered, the agent will have to be thoroughly tested, demonstrating the unlikelihood of significant side effects (Christensen 2001).

There have already been major disappointments regarding "longevity medicines." For example, 2-deoxy-D-glucose (2DG), a compound that inhibits glucose metabolism, proved to have a fatal flaw. Although safe at certain low levels, it apparently becomes toxic for some animals when the amount delivered is raised just a bit or given over long periods. The narrowness of the safety zone bars it from human use, but the work clearly provides a "proof of concept" (that inhibiting glucose metabolism can re-create many effects of caloric restriction) (Lane et al. 2002).

Disheartening reports regarding calorie restriction mimetics makes news from BioMarker Pharmaceuticals even more exciting. BioMarker Pharmaceuticals has discovered that metformin (glucophage) a drug used to treat diabetes can mimic many of the changes in gene expression found in calorie-restricted mice (Kent 2003).

Metformin works from a different prospective than many antidiabetic agents because it does not increase insulin production; rather it lowers the amount of sugar in the bloodstream by decreasing sugar production and absorption and by helping the body respond to its own insulin. Interestingly, metformin was much more effective as a caloric restriction mimetic than either glucotrol (glipizide) which stimulates the pancreas to secrete more insulin or rosiglitazone, which works by making the body less resistant to insulin.

Recall the number of studies that linked the aging process to poor blood glucose control, lack of insulin sensitivity, and hyperinsulinemia (high blood levels of insulin). Yet, it appears that metformin acts beyond glucose regulatory parameters (metformin impacted genes involved in drug metabolism and detoxification, energy metabolism, protein biosynthesis and degradation, cell growth and proliferation, as well as the cytoskeleton). Comment: The cytoskeleton is an internal reinforcement in the cytoplasm of a cell. Microtubules are contained in the cytoskeleton of basically every living cell, providing structure and shape to the cell and a means of intracellular transport. It is purposed that microtubules may act as electrical information processors. When a cell divides, it may pass on genetic information not just in DNA but also in the form of microtubules, which appear integral to cell division mechanics.

Scientists at the National Institute on Aging (NIA) recently reported that metformin increased the life span of mice by 20%. BioMarker Pharmaceuticals is now conducting a life span study using metformin to see if they can replicate the NIA study. For now, the cumulative results of multiple studies push metformin to the "head of the class" in regard to currently evaluated "longevity medicines."

Interventions To Support Longevity

Until "the elixir" is soundly documented, many natural options are available, offering significant "longevity insurance" (alternatives The Life Extension Foundation has recommended to members for decades). For example, The Journal of the American Medical Association (JAMA) recently published that underfed animals (consuming 50% less food) live up to 50% longer, perhaps because of higher levels of dehydroepiandrosterone (DHEA), lower body temperature, and lower insulin levels (JAMA 2002). The following sections address the findings reported in JAMA.

The Glycemic Index and Glycemic Load

Considering a food's glycemic index, as well as glycemic load may prove valuable in keeping blood glucose levels and insulin secretions within a healthy range (a significant factor in attaining longevity). The glycemic index assigns a numerical value to a food indicating how much and how rapidly 50 grams of its carbohydrate content will raise blood sugar levels, compared to 50 grams of a reference food (glucose or white bread). The reference food is given an arbitrary value of 100, and the glycemic index value of a particular food is expressed as a percentage of that value. Many factors contribute to the glycemic index of a given food, including its fat and fiber content and how much it's been processed.

However, the Harvard Women's Health Watch issued a word of warning about applying the glycemic index to your diet: it doesn't say anything about how much carbohydrate a food contains. For example, while the carbohydrates contained in carrots may have a relatively high glycemic index, carrots contain relatively few carbohydrates compared with corn chips. The unfavorable glycemic index rating of carrots (131%) is based on the blood-sugar effect of eating 50 grams of carbohydrate from carrots (the amount contained in a pound and a half), which few people would consume at one setting. Therefore, the net effect of carrots on blood sugar levels is considerably less than corn chips, even though their glycemic index numbers are similar.

The glycemic load is figured by calculating the amount of carbohydrate in a serving of food multiplied by that food's glycemic index. Thus, a -cup serving of carrots (which has 8 grams of carbohydrate) has a glycemic load of about 10 (8 x 131%, or 1.31 = 10.48). Susan Bowerman, assistant director of the UCLA Center for Human Nutrition, advocates assessing the overall glycemic load of the diet and not focusing too much on any one food. For example, increased risk for cardiovascular disease appears to start at a daily glycemic load of about 161 (Harvard Women's Health Watch 2002; Faloon 2002). To peruse the Glycemic Index of approximately 100 foods, please go to Harvard Medical School Health Publications at http://www.health.harvard.edu.

Supplements to Emphasize in Resisting Age-Associated Debility

The classic American daily diet contains about 3,000 calories (men) and 2,000 calories (women). It is subsequently difficult to obtain sufficient nutrients when receiving only 1,500 calories per day. Nutrients often in short supply (in order of scarcity) are: zinc, vitamin E, copper, magnesium, iron, niacin, vitamin B12, pantothenic acid, calcium, riboflavin, folacin, vitamin A, vitamin B6, thiamine, and vitamin C (Best 1995). Thus, a number of supplements may work synergistically with calorie restriction to further tip the odds in favor of longevity.

Continue to Related Supplements . . .


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