Studies in mice boost the reputation of antioxidants as anti-aging agents.
by Craig Weatherby
The healthy reputation of dietary antioxidants just got more support, with one type turning in a spectacular anti-aging performance. The new findings, summarized below, revealed the benefits of two different classes of dietary antioxidants (Click the links to jump down to the stories).
In particular, the startling outcome of the animal study from Harvard holds hope for blunting the public (and personal) health impacts of the current obesity epidemic.
- A Harvard-led team examined the anti-aging effects in mice of resveratrol: a polyphenol-type antioxidant related to the flavonoids and flavanols found in tea, cocoa, nuts, whole grains, and colorful fruits and vegetables.
- A Spanish group studied the immunity-boosting effects in mice of the essential antioxidant nutrients found in most multivitamin pills: vitamins C and E, beta-carotene, zinc, and selenium.
If the Harvard results translate to humans, overweight people may be able increase their lifespan as well as their “health-span” by taking a plant-derived antioxidant. (“Health-span” refers to the number of years someone lives in good health.)
Arguably, the goal of increasing people’s average health-span is a more meaningful one than increasing their average lifespan.
Putting the daily dose in human terms
The obese mice eating a high-fat diet plus resveratrol were consuming very large doses of the anti-fungal anti-cancer antioxidant, equating to 24 milligrams per kilogram (2.2 pounds) of body weight.
Resveratrol supplements typically contain from 10 to 20 mg per capsule, so a 130-lb person would need to take about 94 standard capsules per day, delivering about 1,410 mg of resveratrol, to equal the dose that produced such remarkable results in the mice.
However, in another part of the study, obese mice were given a much lower dose equaling five mg per kilogram per day. They benefited in ways similar to the higher-dose group, but to a lesser extent.
This lower dose level would translate to 295 mg of resveratrol per day for our hypothetical 130-lb person, or about 20 standard resveratrol capsules per day. In fact, Dr. Sinclair and several of his lab associates have been taking daily resveratrol doses equaling five mg per kilogram, with no apparent ill effects.
Fruity red-wine antioxidant keeps obese mice full of life
Since the tide of obesity continues to rise, we can only welcome the results of a new study in mice and hope they translate to humans (Baur JA et al 2006).
A team of researchers from Harvard Medical School and the National Institute on Aging found that high doses of resveratrol—a polyphenol antioxidant especially abundant in red wine—reduced the rate of diabetes, liver problems, and other weight-related problems in obese mice, while extending their lifespans.
Compared with obese mice eating a high-fat diet, obese mice eating a high-fat diet plus resveratrol had 31 percent fewer deaths and lived several months longer: as long as mice on a standard, healthful mouse-chow diet.
What also amazed the researchers was that the organs of the resveratrol-fed obese mice should have shown signs of gross degradation, but instead looked normal.
Despite being on a high-calorie diet, the resveratrol-treated obese mice were about as healthy, agile and active on exercise equipment as their lean counterparts.
According to lead author Dr. David Sinclair of Harvard Medical School, “These fat, old mice can perform as well on this skill test as young, lean mice.”
The cholesterol profiles of the mice on resveratrol didn't improve, but that didn’t seem to affect their overall health.
Grapes, peanuts, and berries are leading food sources of resveratrol (3,5,4´-trihydroxy stilbene), a strong anti-fungal, anti-cancer agent that plants produce in response to microbial attack. Most resveratrol supplements are made from red wine extract or from a Chinese plant called hu zhang (Polygonum cuspidate AKA giant knotweed).
Dr. Sinclair also noted that preliminary findings indicate that resveratrol may extend the lives of slim mice as well. Sinclair is the cofounder of Sirtris Pharmaceuticals Inc., which is testing resveratrol against human diabetes.
The National Institute on Aging found the results so encouraging that it is considering repeating the experiment in rhesus monkeys, since they are a much closer genetic match to humans.
Antioxidant nutrients enhance immunity in mice
Researchers from Madrid’s Complutense University reported that naturally antioxidant-rich cereals and antioxidant-enriched biscuits improved the performance of the immune systems of both healthy and prematurely ageing mice (Alvarez P et al 2006).
In a study published this month, they found that feeding mice any of four cereals—wheat germ, buckwheat flour, fine rice bran, or wheat middlings—for five weeks improved the performance of the animals’ white blood cells (leukocytes).
And the results of a study they published in August give the antioxidant nutrients in most multivitamin-mineral pills credit for boosting immunity in mice.
They divided the mice into two groups, and gave each biscuits containing two different doses of antioxidants (five percent or 20 percent), including vitamins C and E, beta-carotene, zinc, and selenium.
After 15 weeks, the Spanish team measured the performance of the animals’ white blood cells (leukocytes), the strength of their antioxidant defenses, and the levels of oxidative (free radical) damage to the animals’ blood fats and cellular DNA.
The prematurely ageing mice showed the greatest benefit from the antioxidants, and the 20-percent biscuits yielded stronger benefits compared with the five-percent antioxidant biscuits.
The authors noted that previous studies indicated that all of the antioxidants used in the biscuits enhance immune system function in animals and humans.
- Alvarez P, Alvarado C, Mathieu F, Jimenez L, De la Fuente M. Diet supplementation for 5 weeks with polyphenol-rich cereals improves several functions and the redox state of mouse leucocytes. Eur J Nutr. 2006 Oct 11; [Epub ahead of print]
- Alvarado C, Alvarez P, Puerto M, Gausseres N, Jimenez L, De la Fuente M. Dietary supplementation with antioxidants improves functions and decreases oxidative stress of leukocytes from prematurely aging mice. Nutrition. 2006 Jul-Aug;22(7-8):767-77.
- Alvarado C, Alvarez P, Jimenez L, De la Fuente M. Oxidative stress in leukocytes from young prematurely aging mice is reversed by supplementation with biscuits rich in antioxidants. Dev Comp Immunol. 2006;30(12):1168-80. Epub 2006 Apr 21.
- Alvarado C, Alvarez P, Jimenez L, De la Fuente M. Improvement of leukocyte functions in young prematurely aging mice after a 5-week ingestion of a diet supplemented with biscuits enriched in antioxidants. Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1203-10.
- Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature advance online publication 1 November 2006 | doi:10.1038/nature05354; Received 10 August 2006; Accepted 19 October 2006; Published online 1 November 2006.
- Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006 Jun;5(6):493-506. Epub 2006 May 26. Review.