by Bill Gifford
2. “Klatz and Goldman responded by suing”: The lawsuit was widely covered in the media when it was first filed, by, e.g., the Chicago Tribune, Inside Higher Ed, etc.
3. “Adolf Hitler himself”: The drug, and others, was administered by Hitler’s personal physician, Dr. Theodor Morell, and described in his diaries. His steroid use is described in Steroids: A New Look at Performance-Enhancing Drugs, by Rob Beamish (Santa Barbara, CA: Praeger, 2011).
4. “renegade cancer doctors”: Both Stanislaw Burzynski and Richard Gonzalez have lengthy and controversial histories that would take a whole chapter to unpack. In a nutshell, Houston-based Burzynski’s treatments involve administering so-called “antineoplastons,” substances isolated from human urine that he claims can cure many incurable cancers. Because the antineoplastons have not been approved by the FDA (or validated by independent researchers), Burzynski enrolled his patients in clinical trials, allowing them to receive the neoplastons, but FDA inspectors have found numerous problems with his handling of the trials, and have issued multiple warning letters; few if any trial results have ever been published, according to USA Today, which has reported extensively on his activities (e.g., “Doctor accused of selling false hope to cancer patients,” by Liz Szabo, July 8, 2014). New York–based Gonzalez, on the other hand, treats his patients with a complicated regimen of a customized diet, coffee enemas (for “detoxification”) and up to 150 supplements per day. (Sound familiar?) An NIH-sponsored clinical trial of patients with inoperable pancreatic cancer found that patients on Gonzalez’s program lived for an average of 4.3 months, versus 14 months for those on traditional chemotherapy; further, the chemo patients reported a better quality of life. He was the subject of a profile by Michael Specter in the New Yorker, “The Outlaw Doctor,” published February 5, 2001.
5. “Crazy Talk”: Weston Kosova and Pat Wingert, “Why Health Advice on ‘Oprah’ Could Make You Sick,” Newsweek, May 29, 2009. Well worth a read.
6. “the massive Women’s Health Initiative study”: For the original paper, see “Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled Trial.” JAMA.2002;288(3):321-333 (available online free at http://jama.jamanetwork.com/article.aspx?articleid=195120). The study was criticized on many grounds, one of which was that it looked at women who were much older than 50 when they began using hormone replacement, and were thus too old to warrant the increased risk. (The observed benefits of hormone replacement, in the WHI study, included reduced risk of colorectal cancer and hip fractures.) Nevertheless, other major studies of estrogen replacement, in Sweden and in the U.K., found massively increased risk of breast cancer among women taking estrogen and progestin, the usual combination of hormones.
7. “Another thing that tanked”: P. M. Ravdin et al., “The Decline in Breast Cancer Incidence in 2003 in the United States,” New England Journal Medicine 2007 April 19;356(16):1670-4. Nancy Krieger of the Harvard School of Public Health wonders whether the heavy promotion of hormone-replacement therapy by the pharmaceutical industry contributed to the steep rise in breast cancer rates during the 1980s: “Hormone therapy and the rise and perhaps fall of US breast cancer incidence rates: critical reflections.” (International Journal of Epidemiology 2008 June;37(3):627-37). Also, post-WHI, breast cancer rates declined most steeply among the educated, middle- and upper-middle-class white women who were more likely to seek out the treatment (and, after the study, to have then dropped it): N. Krieger et al., “Decline in US breast cancer rates after the Women’s Health Initiative: socioeconomic and racial/ethnic differentials.” (American Journal of Public Health, 2010 April 1;100 Suppl 1:S132-9.)
8. “Actually, not true”: For well-informed (and skeptical) takes on bioidentical hormone therapy, see A. L. Huntley, “Compounded or confused? Bioidentical hormones and menopausal health.” Menopause International 2011 March;17(1):16-8.; and Cirigliano M., “Bioidentical hormone therapy: a review of the evidence.” Journal of Women’s Health 2007 June;16(5):600-31. For an excellent layperson’s summary of the issues around bioidentical hormone treatment, written by two physicians at the Cleveland Clinic, and complete with charts describing FDA-approved bioidentical options, see Lynn Pattimakiel and Holly Thacker, “Bioidentical Hormone Therapy: Clarifying the Misconceptions,” in Cleveland Clinic Journal of Medicine, December 2011 pp. 829-836. The pharmacist’s indictment is described by journalist Sabrina Tavernise in “First Arrest Made in 2012 Steroid Medication Deaths,” New York Times, September 4, 2014.
9. “actual dosages can vary enormously”: e.g., N. A. Yannuzz et al., “Evaluation of compounded bevacizumab prepared for intravitreal injection,” JAMA Ophthalmology. Published online September 18, 2014.
10. “a $2 billion business”: David J. Handelsman, “Global trends in testosterone prescribing, 2000–2011: expanding the spectrum of prescription drug misuse.” Medical Journal of Australia 2013; 199 (8): 548-551.
11. “less prone to lying”: True story. Mathias Wibral et al., “Testosterone Administration Reduces Lying in Men.” PLoS One. 2012; 7(10): e46774. Published online October 10, 2012. The 1941 prostate cancer case was uncovered by Dr. Abraham Morgenthaler, a strong proponent of testosterone therapy and author of books such as Testosterone For Life (New York: McGraw-Hill, 2009). The 2010 study that had to be stopped was S. Basaria et al., “Adverse Events Associated with Testosterone Administration,” New England Journal of Medicine 2010; 363:109-122 July 8, 2010 (available free online at nejm.org). For a good overview of the issues, see this review by researchers at Harvard’s Brigham and Women’s Hospital, who concluded that “a general policy of testosterone replacement in all older men with age-related decline in testosterone levels is not justified”: M. Spitzer et al., “Risks and Benefits of Testosterone Therapy in Older Men,” in Nature Reviews Endocrinology, 2013 April 16. Information on the NIH clinical trial may be found at trial.org.
12. “I love fucking”: Ned Zeman, “Hollywood’s Vial Bodies,” Vanity Fair, March 2012. For the AP investigation, see David B. Caruso and Jeff Donn, “Big Pharma Cashes In On HGH Abuse,” Associated Press, December 21, 2012. Also worth reading is Brian Alexander’s entertaining look at the HGH culture in “A Drug’s Promise (Or Not) of Youth,” Los Angeles Times, July 9, 2006.
13. “frequented by Rodriguez”: Tim Elfrink, “A Miami Clinic Supplies Drugs to Sports’ Biggest Names,” Miami New Times, January 31, 2013.
14. “Mintz had once run”: Christopher McDougall, “What if Steroids Were Good For You?” Best Life, October 2006. Fascinating profile of Drs. Life and Mintz, published just a few months before Mintz’s death.
15. “a single, small study”: Daniel Rudman et al., “Effects of Human Growth Hormone in Men over 60 Years Old,” New England Journal of Medicine, 1990; 323:1-6 July 5, 1990. Thirteen years later, the journal revisited the study in an editorial by Mary Lee Vance, “Can Growth Hormone Prevent Aging?” NEJM 2003; 348:779-780, which noted that other studies had shown that strength training alone conveyed the same benefits that Rudman had observed from HGH: “Going to the gym is beneficial and certainly cheaper than growth hormone.”
16. “a long list of side effects”: See, e.g., Blackman et al., “Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.” JAMA 2002 Nov 13;288(18):2282-92.
17. “growth-hormone ‘knockout’ mice”: The strange longevity of animals that lack growth hormone receptors was first observed by Andrzej Bartke in a strain of naturally-occurring mutant mice called the Ames Dwarf; Bartke and others later created a genetically-engineered version of the Ames that is itself the subject of an extensive scientific literature, which is nicely tied together in this review: Andrzej Bartke, “Growth Hormone and Aging: A Challenging Controversy,” Clinical Interventions in Aging, Dove Press, 2008 December; 3(4): 659–665.
18. “The bigger dogs produce more IGF-1”: Nathan B. Sutter et al., “A Single IGF1 Allele Is
a Major Determinant of Small Size in Dogs,” Science 2007 April 6; 316(5821): 112–115.
19. “It makes me feel good”: “Aging Baby Boomers turn to hormone; some doctors concerned about ‘off-label’ use of drug,” by Sabin Russell, San Francisco Chronicle, November 17, 2003. Three months after the story appeared, she was dead: “Cancer took life of noted user of growth hormone,” by Sabin Russell, San Francisco Chronicle, June 8, 2006.
20. “in 700 years’ time.”: Alex Comfort, The Biology of Senescence 3rd ed. (New York: Elsevier, 1964), 1. This is one of my favorite quotes about aging, and its implications have yet to be fully explored. A few other early gerontologists had attempted parabiosis studies, including Clive McCay, who also discovered the life-extending effect of caloric restriction (aka hunger), but Ludwig’s was by far the largest and most systematic early study. Frederic Ludwig, “Mortality in Syngeneic Rat Parabionts of Different Age,” Transactions of the New York Academy of Sciences 1972 Nov;34(7):582-7.
Chapter 4: Yours Sincerely, Wasting Away
1. “pioneering gerontologist Nathan Shock”: For background on the BLSA, see Nathan W. Shock et al., “Normal Human Aging: The Baltimore Longitudinal Study of Aging,” U.S. Government Printing Office, 1984. It made the papers once in a while, too: Susan Levine, “A New Look at an Old Question: Baltimore research transforms fundamental understanding of aging,” Washington Post, February 10, 1997; and Nancy Szokan, “Study on Aging Reaches Half-century Mark,” Washington Post, December 9, 2008.
2. “most complete medical evaluation that taxpayer money could buy”: Officially, the BLSA is not intended to replace regular checkups with one’s physician, and many of the tests are not considered “diagnostic” in quality, but participants do receive basic results of blood and urine tests, and some others; if study workers detect a potential problem, such as evidence of cancer, they will notify participants.
3. “The slower you walk”: There is much research on the issue of “gait speed” in aging, and many studies link walking pace to mortality rates, as well as disability, nursing-home admission, and other very bad things. Here’s one: S. Studenski et al., “Gait speed and survival in older adults.” JAMA. 2011;305:50-58. Luigi Ferrucci, Eleanor Simonsick, and colleagues tie the evidence together in Schrack et al., “The Energetic Pathway to Mobility Loss: An Emerging New Framework for Longitudinal Studies on Aging,” in Journal of the American Geriatric Society. 2010 October; 58(Suppl 2): S329–S336.
4. “simple handgrip strength in middle age”: Taina Rantanen, Jack Guralnick, et al., “Midlife Hand Grip Strength as a Predictor of Old Age Disability.” JAMA. 1999;281(6):558-560.
5. “a U-shaped curve”: The Economist summarized this research nicely in a 2010 cover story, “The U-Bend of Life: Why, beyond middle age, people get happier as they get older.” December 16, 2010. “Life Begins At 46,” proclaimed the cover.
6. “thousands of Japanese American men in Hawaii”: Bradley J. Willcox et al., “Midlife Risk Factors and Healthy Survival in Men.” JAMA 2006;296:2343-2350.
Chapter 5: How to Live to 108 Without Really Trying
1. “More recently, curcumin”: There is a growing number of studies of curcumin, but the vast majority are in vitro (that is, in the lab dish), or in mice and rats, which do not always equate to human results. What human studies have been done tend to be small, with two dozen subjects or less. For a good overview of human clinical trials to date, see Gupta et al., “Therapeutic roles of curcumin: lessons learned from clinical trials.” AAPS J. 2013 Jan;15(1):195-218.
2. “eight grams of it each day”: One major issue with curcumin has to do with “bioavailability,” how much of the stuff actually gets into our bloodstream; research shows that most of it gets chewed up in the liver, which is one reason my dad takes so much of the stuff. Studies show that you need to take about five grams for it to show up in blood and tissue. Hani et al., “Solubility Enhancement and Delivery Systems of Curcumin an Herbal Medicine: A Review.” Current Drug Delivery, August 25, 2014. More research into the mechanisms of action of curcumin and its effectiveness in human beings is urgently needed.
3. “they’ll reach for a knish”: Rajpathak et al., “Lifestyle Factors of People With Exceptional Longevity,” Journal of the American Geriatrics Society 59:8; 1509-12, published online August 2011.
4. “the men still died sooner”: J. Collerton et al. (2009). “Health and disease in 85 year olds: baseline findings from the Newcastle 85+ cohort study.” British Medical Journal 339: b4904.
5. “Studies of Danish twins”: A. M. Herskind et al., “The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900,” Human Genetics 97(3): 319-323 (1996).
6. “forty-four centenarians”: Barzilai et al., unpublished; personal communication.
7. “the less CETP you have, the better”: A. E. Sanders, C. Wang, M. Katz, et al., “Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene With Memory Decline and Incidence of Dementia.” JAMA 2010;303(2):150-158.
8. “those drugs have not yet panned out”: Pharma blogger and chemist Derek Lowe thinks CETP inhibitors were a bad bet: http://pipeline.corante.com/archives/2013/01/25/cetp_alzheimers_monty_hall_and_roulette_and_goats.php.
9. “One other possible longevity gene had to do with IGF-1”: S. Milman et al. (2014). “Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity.” Aging Cell 13(4): 769-771.
Chapter 6: The Heart of the Problem
1. “six hundred thousand Americans”: According to the Centers for Disease Control, 596,577 died of heart disease in 2011, versus 576,691 of cancer. Cancer is gaining fast, some experts believe, simply because people are surviving heart disease and living longer. http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm.
2. “serious coronary arteriosclerosis”: W. F. Enos et al. (1953). “Coronary disease among United States soldiers killed in action in Korea; preliminary report.” JAMA 152(12): 1090-1093.
3. “a single major risk factor”: D. M. Lloyd-Jones et al. (2006). “Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age,” Circulation 113(6): 791-798.
4. “A major study of 136,000 patients”: A. Sachdeva, C. Cannon et al. “Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations,” in “Get With The Guidelines,” American Heart Journal, January 2009 111-117. Russert’s condition described in “From a Prominent Death, Some Painful Truths,” by Denise Grady, New York Times, June 24, 2008.
5. “certain outward signs of aging”: M. Christoffersen et al. (2014). “Visible age-related signs and risk of ischemic heart disease in the general population: a prospective cohort study.” Circulation 129(9): 990-998. For reaction time, see G. Hagger-Johnson et al. (2014). “Reaction time and mortality from the major causes of death: the NHANES-III study.” PLoS One 9(1): e82959; and of course don’t miss E. Banks et al. (2013). “Erectile dysfunction severity as a risk marker for cardiovascular disease hospitalisation and all-cause mortality: a prospective cohort study.” PLoS Medicine 10(1): e1001372.
6. “ApoB is a much better predictor”: See G. Walldius et al. (2001). “High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study.” Lancet 358(9298): 2026-2033; and also McQueen, M. J., et al. (2008). “Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study.” Lancet 372(9634): 224-233. These are both very large, persuasive studies showing that APoB is a much better predictor than plain vanilla HDL-LDL cholesterol numbers.
7. “Red meat has long been known”: This is a bit controversial, but major studies link red meat consumption not only to heart disease but diabetes and cancer. Most notably, see Colin Campbell’s The China Study (Dallas: BenBella Books, 2005). The TMAO study is small but very inter
esting and has been followed by other studies of meat and the microbiome. R. A. Koeth et al. (2013). “Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.” Nature Medicine 19(5): 576-585. The processed vs. unprocessed question is answered pretty clearly in J. Kaluza et al. (2014). “Processed and unprocessed red meat consumption and risk of heart failure: prospective study of men.” Circulation Heart Failure 7(4): 552-557, which found that unprocessed red meats were not linked to heart failure but processed meats were. (Whew!)
8. “a brand-new condition”: See R. C. Thompson et al. (2013). “Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.” Lancet 381(9873): 1211-1222. The account of Ruffer’s work is from A. T. Sandison, “Sir Marc Armand Ruffer (1859-1917), Pioneer of Paleopathology,” Medical History, April 1967; 11(2): 150–156.
9. “damage from intrinsic aging”: The subject of arterial aging is covered, thoroughly and masterfully, by Ed Lakatta of the National Institute of Aging and colleagues in a series of three papers, beginning with E. G. Lakatta and D. Levy (2003). “Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a ‘set up’ for vascular disease.” Circulation 107(1): 139-146.
Chapter 7: Baldness as Metaphor
1. “Hair loss… affects women, too”: Desmond C. Gan and Rodney D. Sinclair, “Prevalence of Male and Female Pattern Hair Loss in Maryborough,” Journal of Investigative Dermatology Symposium Proceedings (2005) 10, 184–189. Also see M. P. Birch et al., “Hair density, hair diameter, and the prevalence of female pattern hair loss,” British Journal of Dermatology, 2001 Feb;144(2): 297-304. I read this stuff so you don’t have to.
2. “key culprit in hair loss”: L. A. Garza et al. (2012). “Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.” Science Translational Medicine 4(126): 126a–134.