Life Extension Magazine April 2012
Apple Polyphenols and Longevity
By George Randall
In the last year alone, scientists from three different laboratories have published studies that demonstrate how polyphenol molecules derived from apples extend life span in various species by as much as 12%.1-3
These researchers are unraveling the various mechanisms of action that give apple polyphenols such promise as anti-aging nutrients.
Initial findings show that apple polyphenols modulate multiple signaling molecules to delay the onset of age-related disorders. They may also mimic the actions of calorie restriction, a known antiaging technique. One polyphenol, phloridzin, which is heavily concentrated in the skin of the apple, also potently suppresses several processes leading to glycation, another major contributor to aging.
Scientists are discovering why an apple a day may help keep the doctor away.
Recent Longevity Research
In three different labs, scientists conducting initial investigations found that the use of apple polyphenols increased the life span of various species by 10 to 12%.1-3
While these studies are just the beginning of understanding how apple polyphenols contribute to longevity, they all found remarkably consistent results, despite being conducted in three very different species.
The common yeast, S. cerevisiae, is often used in laboratory experiments as a model for understanding the biology of higher organisms because of the great similarity of basic life processes.2 When scientists added the unique apple polyphenol phloridzin to yeast cells in culture, they found that treated cultures lived an average of 2.3 generations longer than control cultures.2
A closer look revealed why. When yeast cultures were treated with apple polyphenols, it toughened the cells’ resistance to oxidative stress, both by inhibiting production of harmful reactive oxygen species and also by ramping up gene expression of vital natural cellular antioxidant systems.2 Furthermore, the yeast cultures increased expression of sirtuins, molecules known to trigger calorie restriction-like effects in multiple tissues, contributing to longevity.
Another common model of aging and longevity is the tiny worm known as C. elegans, which reproduces rapidly and succumbs to many of the same basic destructive processes as do humans. Treatment with apple polyphenols extended the life span of natural C. elegans by 12%.1 As with the previous experiment with apple polyphenols, activation of sirtuins’ calorie restriction-mimicking effects was evident.
Finally, apple polyphenols have been shown to extend by 10% the life span of the fruit fly, D. melanogaster, another commonly-used model of human biological processes and aging.3 Once again, the explanation lies in the activation of a suite of genes that produce natural antioxidant defense systems, and decrease of genes that contribute to death in older animals. Interestingly, in these more complex organisms, apple polyphenols also partially reversed early death and mobility impairment induced by a toxin.3 Loss of mobility is a common characteristic of aging shared across all animal species, and one which is attracting great scientific interest.4
The discovery of such similar results, from three independent laboratories using three different models of biological aging, means that the results are somewhat robust and may be applicable to all living things, humans included. But these encouraging studies only scratch the surface of how apple polyphenols function on multiple levels to delay the aging process and reduce lethal degenerative diseases.
The laboratory investigations discussed above do shed light on why large epidemiological studies show that people who consume polyphenols in the highest quantities are protected against conditions such as cancer, cardiovascular disease, and other conditions that are generated by oxidant stress and inflammation.5-8 For example, those who consumed the largest amounts of flavonoids (found in apples and other fruits) were shown in one study to have up to a 31% reduction in total mortality.9, 10 When intake of apples specifically was examined, that study showed as much as a 43% reduction in death from heart attacks specifically.9
Phloridzin, A Unique Polyphenol
Apples, and especially their skins, contain many of the polyphenols found in other fruits, albeit in considerably higher concentrations.11 Apple skins also contain a polyphenol called phloridzin.12-14 Phloridzin is especially active against glycation, one of the most common, preventable, and reversible causes of aging.
Phloridzin attacks glycation and its destructive effects at many different levels. For example, almost as soon as you consume a carbohydrate-containing meal that could cause a dangerous post-meal spike in blood sugar, phloridzin goes to work. Studies show that phloridzin inhibits glucose uptake by 52%.13,15
Phloridzin accomplishes this feat through two distinct mechanisms in the small intestine. First, it inhibits glucose uptake from the intestine’s interior into its lining cells.15 Subsequently, phloridzin blocks the active transport of glucose out of those intestinal lining cells into the bloodstream.13,15 The net effect is fewer glucose molecules leaving the intestine to contribute to blood sugar levels.
Some sugar, of course, is inevitably absorbed, and is responsible for formation of the dangerous carbonyl molecules that react with proteins and DNA to form advanced glycation endproducts, or AGEs. Phloridzin prevents formation of those carbonyl compounds;16 it also traps any remaining carbonyls that are produced, preventing them from reacting with more vulnerable body molecules.14,16,17 Phloridzin also protects cells from the inside out. In type 2 diabetes, cells don’t efficiently take up glucose, producing dangerous blood sugar elevations that cause so much destruction. But inside certain cells, there’s too little glucose, contributing to energy depletion and poor function. One consequence is cell membrane disruption that contributes to early cell death and ultimately organ dysfunction. Phloridzin protects those energy-depleted cells’ membranes and prevents their death, helping to preserve tissue and organ function.18
The sum of all these effects is prevention of several major causes of aging, including blood glucose elevations and lipid metabolism disturbances.13 The ultimate effect, now demonstrated in laboratory models of aging, is an extension of the life span.13-16,19
Apple Polyphenols’ Unique Fat Management
Various types of fats not only add pounds to our body but can destroy our health by fostering degenerative diseases such cardiovascular disease, diabetes, and cancer. Getting control of how your body handles fat is an important step in reducing your risk of an early death.
Apple polyphenols demonstrate remarkable capabilities of fat management, as shown by a wealth of human, animal, and laboratory studies in two distinct areas.
The first is in where and how your body stores its fat.
Fat in your organs, and especially in the lining of your abdomen (known as visceral fat), is a major risk factor for cardiovascular disease, diabetes, and cancer, as part of the metabolic syndrome.20,21 Apple polyphenols have been shown to reduce visceral fat accumulations in human studies.
In one study, 45 overweight or obese adults were given 600 mg/day of apple polyphenols, and their weight and body fat distribution were tracked for 12 weeks.21 In that time the control patients gained weight, while supplemented patients lost nearly a pound. Of greater importance, the apple polyphenol-supplemented patients lost about 2 square inches of visceral fat area as measured by CT scans, while control patients gained those same 2 square inches of visceral fat, and about 4 square inches of fat overall.
A similarly-designed study using the same 600 mg/day dose followed patients for 16 weeks.22 It demonstrated a 9.4 square-inch loss of visceral fat in supplemented patients, an impressive 8.9% of their baseline area.22 Meanwhile, placebo patients gained 3.3 square inches, or 3.3% of their baseline amount.
Detailed animal studies demonstrate that loss of total and visceral fat can be at least in part attributed to improved fat utilization by energy-requiring tissues such as muscle, helping them to “burn” fat more effectively while increasing muscle strength.23, 24
The second important area of fat management has to do with how your body absorbs triglycerides and cholesterol from your diet, and in what form it transports those fats to your tissues.
Animal studies show that apple polyphenols slow triglyceride absorption from the intestine by blocking pancreatic lipase, an enzyme specifically required to break down triglyceride fats.25,26 Blocking pancreatic lipase causes some triglycerides to pass out of the body in the feces.27 Similar effects in humans could potentially lower total triglyceride levels.27 Apple polyphenols also block cholesterol absorption and interfere with production of the lipoprotein carrier molecules (LDL and VLDL cholesterol) that are associated with cardiovascular risk.28,29
The effects of lowered intestinal fat absorption are lowered plasma levels of LDL, VLDL, and triglycerides (the “bad” fats) by as much as 70%.21,30,31Apple polyphenols also reduce the deposition of fats in organs and in the linings of arteries, where atherosclerosis gets started.30 Animals fed apple polyphenols had up to a 17% reduction in the size of atherosclerotic lesions found in their arteries.32
Apple polyphenols not only lower plasma total and LDL cholesterol, but animal studies show that they have the potential to raise HDL cholesterol levels, further protecting from atherosclerosis.31,33,34 A human study providing 1,500 mg/day of concentrated apple polyphenols demonstrated a modest rise in HDL cholesterol levels, with significant drops in LDL cholesterol.31
One reason that HDL cholesterol is protective is that it is rich in natural antioxidant molecules known as paraoxonases. Apple polyphenols can increase paraoxonase activity by as much as 23%.35 That may explain why apple polyphenols inhibit dangerous lipid peroxidation, the inflammation-generating step that initiates atherosclerosis.
Finally, apple polyphenols lower cardiovascular risk by reducing the “stickiness” of platelets and vessel walls, helping blood slip more readily through arteries.36 That can prevent the formation of dangerous clots.
One cautionary note: Several human studies have failed to show much benefit from consumption of whole apples and even polyphenol-enriched apple juices. One study showed an elevation in triglyceride levels in men who ate whole apples daily for an extended period.37 The reasons aren’t entirely clear, but it is safe to say that the greatest benefits have been shown with concentrated polyphenols derived from apple skins only.