"Long before it's in the papers"
June 04, 2013


Youth” pills, hawked online, win over top scientists

Feb. 9, 2007
By Jack Lucentini
Updated Feb. 12

For cen­turies, shady sales­men have pushed nos­trums claimed to con­quer that eter­nal scourge, ag­ing. Vir­tu­al­ly all have been gar­bage. Chi­na’s king Zhao Mei may have even died from his own “im­mor­tal­ity pills” 2,000 years ago, ar­chae­o­lo­g­ists say.

Pills on the mar­ket are la­beled as con­tain­ing from less than 5 mg to as much as 250 mg of res­ver­a­trol in its ac­tive form. Even that is around one-sixth what an aver­age-weight per­son would have to take dai­ly to get doses com­pa­ra­ble to those used in mouse life-extension stud­ies. But many users are sat­is­fied with tak­ing smaller amounts in or­der to play it safe and save mon­ey.

But one brand of pills hawked on the In­ter­net as con­tain­ing “youth-pro­long­ing” mo­le­cules has a cu­ri­ous dis­tinc­tion. 

A Har­vard Med­i­cal School bi­ol­o­gist who is a lead­ing ex­pe­rt on ag­ing takes them dai­ly, per­suaded by his own re­search that they may work, ac­cord­ing to peo­ple fa­mil­iar with his ac­tiv­i­ties. He also once served as con­sul­tant to the pills’ maker, but said he did so at no charge.

A small but grow­ing band of peo­ple, hear­ing of his use of the pills, has fol­lowed his lead in hopes of liv­ing long­er and more vig­or­ous­ly—as have a di­verse ar­ray of an­i­mals on which the pills’ key in­gre­di­ent has been tested. A No­bel-prize win­ning phys­i­cist counts him­self among the con­verts.

The cap­sules in ques­tion are called Lon­ge­vi­nex (longevinex.com).

The Har­vard re­search­er, Da­vid Sin­clair, has said in in­ter­views that he takes sup­ple­ments con­tain­ing the in­gre­di­ent, called res­ver­a­t­rol. But he wouldn’t spe­ci­fy which of the more than 20 avail­ab­le brands he takes, or ad­vise their use to oth­ers. The med­i­cal school’s rules for­bid do­ing that, an ar­ti­cle in the June 22, 2004 Har­vard Ga­z­ette said.

None­the­less, three peo­ple fa­mil­iar with Sin­clair’s ac­tiv­i­ties said his brand of choice has been Lon­ge­vi­nex.

Grapes and red wine al­so con­tain res­ver­a­trol (see chart), but far too lit­tle for these prod­ucts to con­fer the dra­ma­tic life­span boost seen in an­i­mal stud­ies, re­search­ers say. None­the­less, even mod­er­ate al­co­hol drink­ing is tied to slight­ly high­er life­span in hu­mans, ac­cord­ing to a study in the Dec. 11-25 is­sue of the jour­nal Ar­chives of In­ter­nal Med­i­cine.

But pills may have much more res­ver­a­trol, so some peo­ple want them—though their ef­fects are lit­tle stud­ied, and how the sub­stance works is still de­bated.

Confusion has set in among po­ten­tial buy­ers of these sup­ple­ments, thanks to a slew of com­pet­ing and con­t­ra­dic­to­ry claims from the man­u­fac­tur­ers. The si­lence from Sin­clair, pe­r­haps the best-known re­search­er of res­ver­a­trol’s ef­fects, has­n’t helped. He de­clined to com­ment for this ar­ti­cle. 

Enigmatic tests

A few years ago, Sin­clair con­ducted tests that sug­gested Lon­ge­vi­nex worked far bet­ter than a doz­en com­pet­ing prod­ucts, ac­cord­ing to a news ar­ti­cle in the Feb. 27, 2004 is­sue of the re­search jour­nal Sci­ence. De­tails of the res­ults haven’t been pub­lished or op­ened to the wid­er sci­en­tif­ic com­mu­ni­ty’s scru­ti­ny.

Around then, Sin­clair has said he al­so served as a con­sult­ant to Lon­ge­vi­nex’s maker; all this took place dur­ing the pro­duct’s de­ve­lop­ment, ac­cord­ing to the com­pa­ny pre­si­dent. But Sin­clair an­nounced in a mail­ing at the end of 2003 that he had cut the tie be­cause the com­pa­ny had used his name in pub­li­city. He lat­er launched his own com­pa­ny, Sir­t­ris, to de­vel­op a re­lat­ed pre­scrip­tion prod­uct.

Nonetheless, he keeps tak­ing the pre­s­crip­tion-free Lon­ge­vi­nex, ac­cord­ing to an e­mail at­trib­ut­ed to him by Jus­tin Loew, treas­ur­er of the Im­mor­tal­i­ty In­sti­tute, a San Fran­cis­co-based non-pro­fit group that pro­motes anti-ag­ing re­search.

Last No­vem­ber, Loew said in an on­line fo­rum that Sin­clair had e­mailed him: “I take 4 pills of lon­ge­vi­nex with bfast and 4 at din­ner, but I don’t rec­om­mend an­y­one else take any res­ver­a­trol pills un­til we know more.” (Note: late last month, the man­u­fac­tur­er raised the amount of res­ver­a­trol per cap­sule, so Sin­clair’s re­ported eight pills would be equi­va­lent to 3.2 now. Ei­ther way, his re­port­ed re­gi­men amounts to about 320 mg dai­ly. Three pills daily would cost about $3.50 a day cur­rent­ly.)

Bill Sardi, pres­ident of Res­ver­a­trol Part­ners LLC, maker of Lon­ge­vi­nex, con­firmed Loew’s ac­count. Sin­clair told The New York Times in ear­ly No­vem­ber that he has used res­ver­a­trol for three years—about the same length of time Lon­ge­vi­nex has ex­isted. He added that his wife, par­ents, and ‘‘half my lab’’ of two doz­en mem­bers pop res­ver­a­trol too.

To some ob­servers, the bets Sin­clair makes for his own body are far more per­sua­sive than any rec­om­mendations or non-rec­om­mend­a­tions he might have for the rest of us. “Sin­clair is a Har­vard dude, okay?” one user of the Web fo­rum wrote. “We can de­bate all day, but the proof that the guy takes the stuff is good enough for me.”

A si­m­i­lar sen­ti­ment, ex­pressed more re­served­ly, came from a 2004 No­bel Lau­re­ate in physics, Frank Wilczek of the Mas­sa­chu­setts In­sti­tute of Tech­nol­o­gy in Cam­bridge, Mass. He said he takes Lon­ge­vi­nex. That Sin­clair uses it was “cer­tainly one of the things that im­pressed me,” he added, as did a re­cent study on res­ver­a­trol by Sin­clair in the re­search jour­nal Na­ture. While not a bio­lo­gist, “I know how to read cri­ti­cal­ly,” Wilczek added; as far as the pills go, “there does­n’t seem to be much pos­si­ble down­side, and the up­side is very con­si­der­able.”

Not ever­yone agrees. 

A downside?

“The right place now with res­ver­a­trol is to say that this is real­ly in­tri­guing da­ta, but mice aren’t hu­mans,” Brent Bau­er, di­rec­tor of the com­ple­men­ta­ry and in­te­gra­tive med­i­cine pro­gram at the Mayo Clin­ic in Roch­es­ter, Minn., told The Wall Street Jour­nal in late No­vem­ber, af­ter the lat­est spate of ma­jor res­ver­a­trol stud­ies were pub­lished.

“Do we know the right dos­age? No. Do we know the side ef­fects? No. Do we know if there are po­ten­tial con­tam­i­nants? No,” said Tod Coope­rman, pres­ident of consumerlab.com, a pro­vid­er of in­de­pend­ent test re­sults, in a Na­tion­al Pub­lic Ra­di­o in­ter­view in No­vem­ber. “Per­son­ally, I would wait.”

Res­ver­a­trol has been tied to both great­er life­span and vig­or in an­i­mals. Since 2003, it has been found to ex­tend life­span in worms and flies by near­ly 30 pe­rcent; fish and yeast by al­most 60 pe­rcent; and obese mice by an es­ti­mat­ed 15 pe­rcent, though that stu­dy, by Sin­clair and col­leagues, is un­fin­ished. 

Hope that hu­mans might ben­e­fit sim­i­larly stems from the con­sist­en­cy of the an­i­mal re­sults, and the fact that hu­mans and other an­i­mals are ge­net­i­cal­ly close­ly re­lat­ed. Nine­ty-nine pe­rcent of genes are si­m­i­lar in mice and hu­mans, for ex­am­ple. 

But res­ver­a­trol’s ef­fects on hu­man life­span are un­known be­cause our rel­a­tively long life­spans make stud­ies dif­fi­cult. Some an­ec­do­tal re­ports have suf­ficed to raise eye­brows, though. Sardi said some us­ers of his pro­duct have re­ported some re­ver­sal of hair gray­ing. An ed­i­tor of World Sci­ence (which has no ties to anyone sel­ling res­ver­a­trol) tried it and ex­per­i­enced the same thing.

As far as ill effects, re­search­ers say the jury is out, but no­thing has raised alarms yet. “About 10,000 peo­ple in this coun­try take this prod­uct with no ap­par­ent side ef­fects,” the Har­vard Ga­zette ar­ti­cle quoted Sin­clair say­ing.

Compared to what Sin­clair re­portedly takes, fish and mice in the lon­gev­i­ty stud­ies got doses rough­ly five to se­ven times high­er—ad­just­ing for their weight—with no re­ported prob­lems. In rat stud­ies, re­search­ers found that they had to mul­t­i­ply those high­er doses again, by some­where be­tween 10 and 30, for harm­ful ef­fects to become evi­dent. But no long-term safe­ty stud­ies have been done in hu­mans, or with spe­cif­ic com­mer­cial prod­ucts. Sardi re­com­mends that his not be taken by grow­ing chil­dren or preg­nant wo­men, or sim­ul­ta­neous­ly with other med­i­ca­tions.

Just why Sin­clair’s tests evi­dent­ly fa­vored Sar­di’s prod­uct is un­clear. Sar­di has com­missioned some tests of his own, with si­mi­lar re­sults, but us­ing a meth­o­dol­ogy whose mer­its sci­ent­ists have since de­bated.

Sar­di says his ad­van­tage is that his cap­sules are spe­cial­ly made to keep the mo­le­cule stable, and com­pe­ti­tors’ aren’t. But a June 2005 study in the jour­nal Chem­i­cal and Phar­ma­ceu­ti­cal Bul­let­in tested five com­pe­t­ing brands and found that they con­tained close to the la­beled amounts of res­ve­r­a­t­rol; the mak­ers ap­pa­rent­ly hadn’t lied about the con­tent. Sar­di coun­ters that his and Sin­clair’s tests as­sessed not only the res­ver­a­trol con­tent, but its bio­lo­g­i­cal ac­t­i­vity. The is­sue re­mains un­re­solved.

James Betz—a com­pet­i­tor of Sardi’s and gen­er­al ma­na­ger of Bio­ti­via Bio­ceu­ti­cals (bioflu.com)—said he be­lieves Sardi and Sin­clair may have, or have had, a “fi­nan­cial re­la­tion­ship.”

Sin­clair wrote in his 2003 mail­ing that he “never re­ceived any mon­ey” from Sar­di’s firm. But he did­n’t say whe­ther he might have been com­pen­sated in other ways, such as dis­count­ed pills. Was he? Sardi, asked that this week, be­came en­raged and re­fused to an­s­wer. His company lawyer, Tracy Au­gus­tine, said there was no com­pen­sa­tion of any kind, and that Sar­di may have reacted ang­ri­ly be­cause “He hears that all the time... At some point it got to him.”

Oth­er mar­keters of resveratrol supplements include Bi­o­ti­via, which boasts the high­est res­ver­a­trol con­tent per pill; and—among those whose res­ver­a­trol con­tent was veri­fied in the 2005 study—Food Sci­ence of Ver­mont (fslabs.com); Nu­tra­ceu­ti­cal (nutraceutical.com) and Source Nat­u­rals (sourcenaturals.com).

* * *

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For centuries, salesmen have pushed nostrums that claim to conquer that eternal scourge, aging. Virtually all of them have been useless, or worse. China’s king Zhao Mei may have died from his own “immortality pills” 2,000 years ago, archaeo logists say. But one brand of pills hawked on the Internet as containing “youth-prolonging” molecules has a curious distinction: a Harvard Medical School biologist who is a leading expert on aging takes them daily, according to people familiar with his activities. So does a Nobel-prize winning physicist. The Harvard researcher’s personal choice has persuaded a small but growing number of other people to follow his example, in hopes of living longer and more vigorously—as have the varied animal species on which the pills’ key ingredient has been tested. The capsules in question are called Longevinex (longevinex.com). The Harvard researcher, David Sinclair, has acknowledged in interviews that he takes pills containing the ingredient, called resveratrol; but has refused to say which brand, or to advise their use to others. More than 20 brands of pills are marketed as containing resveratrol. Nonetheless, three people familiar with Sinclair’s activities said his brand of choice has been Longevinex. His silence on the specifics is due to pressure from Harvard, added Bill Sardi, president of Resveratrol Partners LLC, which makes the capsules. Grapes and red wine also contain resveratrol, but far too little (see chart) for these to confer the sizeable lifespan boost seen in animal studies. Nonetheless, even moderate alcohol drinking is tied to slightly higher lifespan in humans, according to a study in the Dec. 11-25 issue of the journal Archives of Internal Medicine. But pills may have much more resveratrol, so some people want them—though their effects haven’t been studied, and how resveratrol works is still debate. Widespread confusion afflicts these potential buyers thanks to a barrage of competing claims from the many manufacturers of resveratrol pills. The silence from Sinclair, perhaps the best-known researcher of resveratrol’s effects, hasn’t helped. He declined to comment for this article. A few years ago, Sinclair conducted tests that strongly suggested Longevinex worked better than a dozen competing products, according to a news article in the Feb. 27, 2004 issue of the research journal Science. The test’s details haven’t been published or subjected to scrutiny from the wider scientific community. Sinclair also briefly worked for Longevinex as a consultant around that time. He quit at the end of 2003, claiming the company had used his name without permission; he later launched his own company, Sirtris, to develop a related prescription product. Yet he keeps taking Longevinex, according to an email attributed to him and forwarded by Justin Loew, treasurer of the Immortality Institute, a San Francisco-based non-profit group that promotes research on fighting aging. Last November, Loew reported in an online forum that Sinclair had emailed him: “I take 4 pills of longevinex with bfast and 4 at dinner, but I don’t recommend anyone else take any resveratrol pills until we know more.” (Last month, the manufacturer boosted the amount resveratrol per capsule. Sinclair’s reported eight pills are equivalent to 3.2 with the new dosage; either way, the regimen amounts to 320 mg daily.) Sardi said Sinclair indeed takes Longevinex, and is one of a growing number of users. Sinclair told the New York Times in early November that he has taken resveratrol for three years, which is about the same amount of time Longevinex has existed. He added that his wife, parents, and ‘‘half my lab’’ of two dozen members do so too. To some observers, the bets Sinclair is making for his own body speak far more persuasively than any recommendations or non-recommendations he might have for the rest of us. “Sinclair is a Harvard dude, okay?” one user of the Web forum wrote. “We can debate all day, but the proof that the guy takes the stuff is good enough for me.” A similar sentiment came from 2004 Nobel Prize Laureate Frank Wilczek, or the Massachusetts Institute of Technology in Cambridge, Mass. “It’s true, I take it,” he said of Longevinex. That Sinclair uses it was “certainly one of the things that impressed me,” he added, as did Sinclair’s recent papers on resveratrol in the research journal Nature. “There doesn’t seem to be much possible downside, the upside is very con siderable,” Wilczek said of the pills. Not everyone agrees. “The right place now with resveratrol is to say that this is really intriguing data, but mice aren’t humans,” Brent Bauer, director of the complementary and integrative medicine program at the Mayo Clinic in Rochester, Minn., told the Wall Street Journal in late November, after the latest spate of major resveratrol studies were published. “Do we know the right dosage? No. Do we know the side effects? No. Do we know if there are potential contaminants? No,” said Tod Cooperman, president of consumerlab.com, a provider of independent test results, on a National Public Radio interview in November. “Personally, I would wait.” Resveratrol has been tied to both greater lifespan and vigor in animals. Since 2003, it has been found to extend lifespan in worms and flies by nearly 30 percent; fish and yeast by almost 60 percent; and obese mice by an estimated 15 percent, though that study, by Sinclair and colleagues, is unfinished. Hope that humans might benefit similarly stems from the consistency of the animal results, and the fact that humans and animals are genetically closely related. Ninety-nine percent of genes are similar in mice and humans, for example. But resveratrol’s effects on human lifespan are unknown because our relatively long lifespans makes the studies difficult. Some anecdotal reports have sufficed to raise eyebrows, though. For instance, some users have reported partial reversal of hair graying with resveratrol—something also experienced by an editor of World Science, which has no ties to any resveratrol manufacturers. There is “little evidence” of any ill effects of resveratrol, Sinclair wrote in the June issue of the research journal Nature Reviews Drug Discovery. The fish and mice in the longevity studies got doses some five to seven times higher than what Sinclair reportedly takes—adjusting for their weight—with no reported ill effects. In rat studies, researchers found that harmful effects of resveratrol appeared only with doses somewhere between 10 and 30 times those used in the longevity studies, again weight-adjusted. But no safety studies have been done in humans, or with specific commercial products such as Longevinex. Other marketers of resveratrol supplements include Biotiva (bioflu.com), which boasts the highest resveratrol content per pill; and—among a few that had their resveratrol content confirmed in a June 2005 study in the journal Chemical and Pharmaceutical Bulletin—Food Science of Vermont (fslabs.com); Nutraceutical (nutraceutical.com) and Source Naturals (sourcenaturals.com).