1 A. M. Cunningham. 2003. “BioBots.” ScienCentralNews; www.sciencentral.com/articles/view.php3?
article_id5218391960&language5English; A. Moore. 2001. “Of
silicon and submarines.” EMBO Reports. 2(5): 367–370; www.nature.com/cgi-taf/DynaPage.taf?file5/embor/journal/v2/n5/full/embor411.html.
2 “Purdue researchers connect life’s blueprints with its
energy source.” Purdue News, February 4, 2003; http://news.uns.purdue.edu/html4ever/030204.Guo.ATP.html.
3 “Today at UCI.” May 8, 2003; http://today.uci.edu/news/release_detail.asp?key5995.
4 R. Kurzweil. “The Law of Accelerating Returns.” KurzweilAI.net.
meme/frame.html?main5/articles/art0134.html; R. Kurzweil. 2005 (upcoming).
The Singularity Is Near: When Humans Transcend Biology. New York: Viking
5 Ray Kurzweil’s theory of the “law of accelerating returns,”
and its social and economic impact, was introduced in The Age of Spiritual
Machines (Viking, 1999) and will be further explored in his upcoming
book The Singularity Is Near: When Humans Transcend Biology (Viking,
6 R. N. Anderson. The Ten Leading Causes of Death in the U.S., Final
2000 Data. Heart Disease: 710,760, Cancer: 553,091, Stroke: 167661,
Chronic Lower Respiratory Disease: 122,009, Accidents: 97,900, Diabetes:
69,301, Pneumonia/Influenza: 65,313, Alzheimer’s Disease: 49,558,
Nephritis, nephrotic syndrome, and nephrosis: 37,251, Septicemia: 31,224.
7 J. C. Riley. 2001. Rising Life Expectancy: A Global History. Cambridge:
Cambridge University Press.
8 F. Fukuyama. 2002. Our Posthuman Future: Consequences of the Biotechnology
Revolution. New York: Farrar Straus.
9 The U.S. Department of Agriculture’s “Food Pyramid”
can be viewed at www.nal.usda.gov:
8001/py/pmap.htm. The emphasis on starches and grains at the base of
the pyramid has been linked with the current “epidemic”
of obesity plaguing our country.
10 R. N. Anderson. National Vital Statistics Report, 2002 (Sept 16);50:16:
1–86. Also, according to the Minneapolis Heart Institute Foundation,
“Approximately two-thirds of heart attacks are first heart attacks
and one-third of all heart attacks are fatal. The first symptom of heart
attack is often sudden death.” See www.mplsheartfoundation.org.
11 L. A. Ries et al., eds. SEER Cancer Statistics Review, 1973–1999,
National Cancer Institute, Bethesda, Maryland. For example, the Alliance
for Lung Cancer Fact Sheet states that, due to a lack
of screening, lung cancer is diagnosed in the late stages up to 85 percent
of the time; www.alcase.org/factsabout_lungcancer.html. Late-stage diagnosis
occurs in close to half of all cervical cancer occurrences. J. M. Ferrante
et al. 2000. “Clinical and Demographic Predictors of Late-Stage
Cervical Cancer, Arch Fam Med. 9: 439–445. And, over 50 percent
of all cases of ovarian cancer are diagnosed in late stages. A. Srikameswaran.
“Experts discuss promising new test for ovarian cancer.”
Pittsburgh Post-Gazette. May 7, 2002.
12 The Recommended Dietary Allowances were first issued in 1968 by the
National Academy of Sciences and were last revised in 1989. These standards
vary depending on age, gender, and whether a woman is pregnant or lactating.
They are not designed to be “optimal” but rather to avoid
specific nutritional deficiency diseases. They are expressed as average
daily intakes over time. They rely on dietary sources rather than vitamin
or mineral supplementation, and do not account for unusual requirements
disease or environmental stress. See www.blionline.com/HDB/NutritionalStandardsRDAUSRDAAnd
13 O. W. Rasmussen et al. 1993. “Effects on blood pressure, glucose
and lipid levels of a high-monounsaturated fat diet compared with a
high-carbohydrate diet in NIDDM subjects.” Diabetes Care. 16:
14 On the Web site for the American Diabetes Association is found the
“Diabetic Food Pyramid.” Interestingly, it is essentially
identical to the Department of Agriculture’s Food Pyramid recommended
for the general public. The same reliance on a starch- and grain-based
diet with 30 percent of calories coming from fat is recommended. See
15 D. Ornish. “Can lifestyle changes reverse coronary heart disease?”
1990. Lancet. 336: 129–133.
16 E. G. Vermeulen et al. 2000. “Effect of homocysteine-lowering
treatment with folic acid plus vitamin B6 on progression of sub clinical
atherosclerosis: a randomized, placebo-controlled trial.” Lancet.
Feb 12;355(9203): 517–522. Also, in an editorial accompanying
A. D. Korczyn. 2002. “Homocysteine, Stroke, and Dementia,”
Stroke. 33: 2343–2344, Dr. Korczyn of Tel-Aviv University Medical
School in Ramat-Aviv, Israel, says, “Since dietary habits are
so different among people, it may be appropriate to recommend 2 to 5
mg folic acid and a similar dose of vitamin B12 daily. This recommendation
is based on the known safety of both vitamins, which do not have side
effects even if used in excessive amounts, and their low cost.”
1 Nanotechnology is “thorough, inexpensive control of the structure
of matter based on molecule-by-molecule control of products and byproducts;
the products and processes of molecular manufacturing, including molecular
machinery.” (E. Drexler and C. Peterson. 1991. Unbounding the
Future: The Nanotechnology Revolution. New York: William Morrow and
Company.) According to the authors (chapter 1): “Technology has
been moving toward greater control of the structure of matter for millennia
. . . [P]ast advanced technologies—microwave tubes, lasers, superconductors,
satellites, robots, and the like—have come trickling out of factories,
at first with high price tags and narrow applications. Molecular manufacturing,
though, will be more like computers: a flexible technology with a huge
range of applications. And molecular manufacturing won’t come
trickling out of conventional factories as computers did; it will replace
factories and replace or upgrade their products. This is something new
and basic, not just another twentieth-century gadget. It will arise
out of twentieth-century trends in science, but it will break the trend-lines
in technology, economics, and environmental affairs.”
Drexler and Peterson outline the following possible scenarios to explain
the scope of the revolution: efficient solar cells “as cheap as
newspaper and as tough as asphalt,” molecular mechanisms that
can kill cold viruses in six hours before biodegrading, immune machines
that destroy malignant cells in the body at the push of a button, pocket
supercomputers, the end of the use of fossil fuels, space travel, and
restoration of lost species. Also see another book by K. E. Drexler,
Engines of Creation (Anchor Books, 1986). Foresight Institute has a
useful list of nanotechnology FAQs (www.foresight.org/NanoRev/FIFAQ1.html)
and other information. Other Web resources include the National Nanotechnology
Initiative (www.nano.gov), www.
nanotechweb.org, Dr. Ralph Merkle’s Nanotechnology page (www.zyvex.com/nano/),
and Nanotechnology (an online journal: www.iop.org/EJ/journal/0957-4484).
Extensive material on nanotechnology can be found on Ray Kurzweil’s
Web site, www.kurzweilai.net.
2 Nanotechnology is technology in which objects are built from individual
atoms or molecules, or where one or more dimensions are on a scale of
nanometers (billionths of meter). For further information, see K. E.
Drexler’s 1986 classic Engines of Creation; www.kurzweilai.net/meme/frame.html?m58.
3 Besides the functions of different types of cells, two other causes
for cells to control the expression of genes are environmental cues
and developmental processes. Even simple organisms such as bacteria
can turn on and off the synthesis of proteins, depending on environmental
cues. E. coli, for example, can turn off the synthesis of proteins that
allow it to fix nitrogen gas from the air when there are other, less-energy-intensive
sources of nitrogen in its environment. A recent study of 1,800 strawberry
genes found that the expression of 200 of those genes varied during
different stages of development (E. Marshall. 1999. “An array
of uses: expression patterns in strawberries, Ebola, TB, and mouse cells.”
Science. 286(5439): 445).
4 Along with a protein-encoding region, genes include regulatory sequences
called promoters and enhancers that control where and when that gene
is expressed. Promoters are located “upstream” (on base
pairs nearby the transcription site) on the DNA molecule. An enhancer
activates a promoter, thereby controlling the rate of gene expression.
To be expressed, most genes require enhancers; enhancers determine when
genes are expressed and for which target protein cell type. Each gene
can have several different enhancer sites linked to it (S. F. Gilbert.
2000. Developmental Biology, 6th ed. Sunderland, Massachusetts: Sinauer
Associates; searchable online at www.ncbi.nlm.nih.gov/books/bv.fcgi?call5bv.View..ShowTOC&rid5dbio.TOC&depth52.
By binding to enhancer or promoter regions, transcription factors start
or repress the expression of a gene. New knowledge of transcription
factors has transformed our understanding of gene expression. Per S.
F. Gilbert in the chapter “The Genetic Core of Development: Differential
Gene Expression,” “The gene itself is no longer seen as
an independent entity controlling the synthesis of proteins. Rather,
the gene both directs and is directed by protein synthesis. Natalie
Anger (1992) has written, ‘A series of discoveries suggests that
DNA is more like a certain type of politician, surrounded by a flock
of protein handlers and advisors that must vigorously massage it, twist
it and, on occasion, reinvent it before the grand blueprint of the body
can make any sense at all.’”
5 Many antisense RNAs “have shown convincing in vitro reduction
in target gene expression and promising activity against a wide variety
of tumors.” A. Biroccio, C. Leonetti, and G. Zupi. 2003. “The
future of antisense therapy: combination with anticancer treatments.”
Oncogene. Sep 29;22(42): 6579–6588. See also “Subtle gene
therapy tackles blood disorder.” October 11, 2002, NewScientist.com;
newscientist.com/news/news.jsp?id-ns99992915; X. Jiang et al. 2003.
“Inhibition of MMP-1 expression by antisense RNA decreases invasiveness
of human chrondrosarcoma.” J Orthop Res. Nov;21(6): 1063–1070.
6 B. Holmes. “Gene therapy may switch off Huntington’s.”
NewScientist.com, March 13, 2003; www.newscientist.com/news/news.jsp?id5ns99993493.
“Emerging as a powerful tool for reverse genetic analysis, RNAi
is rapidly being applied to study the function of many genes associated
with human disease, in particular those associated with oncogenesis
and infectious disease.” J. C. Cheng, T. B. Moore, and K. M. Sakamoto.
2003. “RNA interference and human disease.” Mol Genet Metab.
Oct;80(1–2): 121–128. RNAi is a “potent and highly
sequence-specific mechanism” (L. Zhang, D. K. Fogg, and D. M.
Waisman. 2003. “RNA interference-mediated silencing of the S100A10
gene attenuates plasmin generation and invasiveness of Colo 222 colorectal
cancer cells.” J Biol Chem. Oct 21 [e-pub ahead of print]).
7 Gene transfer to somatic cells affects a subset of cells in the body
for a period of time. It is theoretically possible to also alter genetic
information in egg and sperm (germ line) cells, for the purpose of passing
on those changes to the next generations. Such therapy poses many ethical
concerns and has not yet been attempted.
8 Genes encode proteins, which perform vital functions in the human
body. Abnormal or mutated genes encode proteins that are unable to perform
those functions, resulting in genetic disorders and diseases. The goal
of gene therapy is to replace the defective genes so that normal proteins
are produced. This can be done in a number of ways, but the most typical
way is to insert a therapeutic replacement gene into the patient’s
target cells using a carrier molecule called a vector. “Currently,
the most common vector is a virus that has been genetically altered
to carry normal human DNA. Viruses have evolved a way of encapsulating
and delivering their genes to human cells in a pathogenic manner. Scientists
have tried to take advantage of this capability and manipulate the virus
genome to remove the disease-causing genes and insert therapeutic genes.”
(Human Genome Project, “Gene Therapy,” www.ornl.gov/TechResources/Human_Genome/
medicine/genetherapy.html). See the Human Genome Project site for more
information about gene therapy and links. Gene therapy is an important
enough area of research that there are currently six scientific peer-reviewed
gene therapy journals and four professional associations dedicated to
9 K. Smith. 2002. “Gene transfer in higher animals: theoretical
considerations and key concepts.” J Biotechnol. Oct 9;99(1): 1–22.
10 “‘Miracle’ gene therapy trial halted.” NewScientist.com,
October 3, 2003; www.newscientist.
com/news/news.jsp?id5ns99992878; Human Genome Project. “Gene therapy,”
11 L. Wu, M. Johnson, and M. Sato. 2003. “Transcriptionally targeted
gene therapy to detect and treat cancer.” Trends Mol Med. Oct;9(10):
12 S. Westphal. “Virus synthesized in a fortnight.” NewScientist.com,
November 14, 2003; www.
13 A. Ananthaswamy. “Undercover genes slip into the brain.”
NewScientist.com, March 20, 2003; www.newscientist.com/news/news.jsp?id5ns99993520.
14 A. E. Trezise et al. 2003. “In vivo gene expression: DNA electrotransfer.”
Curr Opin Mol Ther. Aug;5(4): 397–404.
15 S. Westphal. “DNA nanoballs boost gene therapy.” NewScientist.com,
May 12, 2002; www.
16 B. Dekel et al. 2003. “Human and porcine early kidney precursors
as a new source for transplantation.” Nature Med. Jan 1;(9): 53–60.
17 Here is one possible explanation: “In mammals, female embryos
have two X-chromosomes and males have one. During early development
in females, one of the X’s and most of its genes are normally
silenced or inactivated. That way, the amount of gene expression in
males and females is the same. But in cloned animals, one X-chromosome
is already inactivated in the donated nucleus. It must be reprogrammed
and then later inactivated again, which introduces the possibility of
errors.” “Genetic defects may
explain cloning failures.” CBCNews, May 27, 2002; www.cbc.ca/storview/CBC/2002/05/27/
cloning_errors020527. That story reports on F. Xue et al. 2002. “Aberrant
patterns of X chromosome inactivation in bovine clones.” Nat Genet.
18 J. B. Gurdon and A. Colman. 1999. “The future of cloning.”
Nature. 402: 743–746; G. Stock and J. Campbell, eds. 2000. Engineering
the Human Germline: An Exploration of the Science and Ethics of Altering
the Genes We Pass to Our Children. New York: Oxford University Press.
19 W. S. Hwang. 2004. “Evidence of a Pluripotent Human Embryonic
Stem Cell Line Derived from a Cloned Blastocyst.” Science. Mar
20 G. Vince. “Nanotechnology may create new organs.” NewScientist.com,
July 8, 2003; www.
21 S. Westphal. “‘Virgin birth’ method promises ethical
stem cells.” NewScientist.com, April 3, 2003; www.newscientist.com/news/news.jsp?id5ns99993654.
22 Liver stem cells have been transformed into pancreatic cells (L.
Yang et al. 2002. “In vitro trans-differentiation of adult hepatic
stem cells into pancreatic endocrine hormone-producing cells.”
Proc Natl Acad Sci USA. Jun 11;99(12): 8078–8083). Adult muscle
stem cells can be transformed into muscle, neural tissue, and blood
vessels. Z. Qu-Petersen et al. 2002. “Identification of a novel
population of muscle stem cells in mice: potential for muscle regeneration.”
J Cell Biol. May;157: 851–864.
23 A. M. Hakelien et al. 2002. “Reprogramming fibroblasts to express
T-cell functions using cell extracts.” Nature Biotechnology. May;20:
24 See the description of transcription factors in note 3, page 380.
25 R. P. Lanza et al. 2000. “Extension of cell life-span and telomere
length in animals cloned from senescent somatic cells.” Science.
Apr 28;288(5466): 665–669. See also J. C. Ameisen. 2002. “On
the origin, evolution, and nature of programmed cell death: a timeline
of four billion years.” Cell Death & Differentiation. Apr;9(4):
367–393; M. E. Shay. “Transplantation without a donor.”
Dream: The magazine of possibilities, Children’s Hospital Boston,
Fall 2001; www.childrenshospital.org/about/dreamfall01.pdf.
26 S. Bhattacharya. “Stem cell ‘immortality’ gene
found.” NewScientist.com, May 30, 2003; www.
27 A. D. de Grey. 2003. “The foreseeability of real anti-aging
medicine: focusing the debate.” Exp Gerontol. Sep;38(9): 927–934;
A. D. de Grey. 2003. “An engineer’s approach to the development
of real anti-aging medicine.” Sci SAGE KE. Jan 8;2003(1): VP1;
A. D. de Grey et al. 2002. “Is human aging still mysterious enough
to be left only to scientists?” Bioessays. Jul;24(7): 667–676.
28 A. D. de Grey. “Engineering negligible senescence: rational
design of feasible, comprehensive rejuvenation biotechnology,”
29 A. D. de Grey et al. 2004. “Total deletion of in vivo telomere
elongation capacity: an ambitious but possibly ultimate cure for all
age-related human cancers.” Annals NY Acad Sci. 1019: 147–170.
30 O. J. Finn. 2003. “Cancer vaccines: between the idea and the
reality.” Nat Rev Immunol. Aug;3(8): 630–641; R. C. Kennedy
and M. H. Shearer. 2003. “A role for antibodies in tumor immunity.”
Int Rev Immunol. Mar–Apr;22(2): 141–172.
31 A. D. de Grey. 2002. “The reductive hotspot hypothesis of mammalian
aging: membrane metabolism magnifies mutant mitochondrial mischief.”
Eur J Biochem. Apr;269(8): 2003–2009; P. F. Chinnery et al. 2002.
“Accumulation of mitochondrial DNA mutations in ageing, cancer,
and mitochondrial disease: is there a common mechanism?” Lancet.
Oct 26;360(9342): 1323–1235; A. D. de Grey. 2000. “Mitochondrial
gene therapy: an arena for the biomedical use of inteins.” Trends
Biotechnol. Sep;18(9): 394–399.
32 S. Graham. “Methuselah worm remains energetic for life.”
ScientificAmerican.com, October 27, 2003; www.sciam.com/article.cfm?chanID5sa003&articleID5000C601F-8711-1F99-86FB83414B7F0156.
33 P. Ball and H. Pearson. “Drug may give cells a fresh start.”
Nature Science Update, January 30, 2004; www.nature.com/nsu/040126/040126-14.html.
34 H. Pearson. “Instant stem cells—just add water.”
Nature Science Update, December 19, 2003; www.nature.com/nsu/031215/031215-11.html.
35 R. A. Freitas Jr. Nanomedicine, Volume I: Basic Capabilities, first
in an anticipated four-volume Nanomedicine technical book series. Freitas
offers a pioneering and fascinating glimpse into a molecular-nanotechnology
future with far-reaching implications for the medical profession—and
ultimately for the radical improvement and extension of natural human
biological structure and function.
36 Sensors and diagnostic tools are important applications of nanotechnology
because the devices can be placed in direct contact with cells and the
molecules in it. Another option is nanoimaging, in which nanocrystals
would seek out different types of molecules, such as cancer cells. When
stimulated by a laser, the crystals would emit light. These applications
are just the “tip of the nano-iceberg” (P. Balasubramanian
and S. Japa. 2003. “Nanosensing,” Stanford Biomedicine Quarterly.
Spring, p. 13).
37 For activities of the International Society for BioMEMS and Biomedical
Nanotechnology, see its site (www.bme.ohio-state.edu/isb/). You can
also find BioMEMS conferences listed on the SPIE site (www.spie.org/Conferences).
38 As reported in the Stanford Biomedicine Quarterly article in note
36 above, researchers used a gold nanoparticle to monitor blood sugar
in diabetics. Y. Xiao et al. 2003. “‘Plugging into enzymes’:
Nanowiring of redox enzymes by a gold nanoparticle.” Science.
Mar 21;299(5614): 1877–1881. “One might even speculate on
the design of an ‘artificial pancreas,’ an implant that
would release appropriate levels of insulin into the blood from moment
to moment according to the blood sugar readings provided by this nanosensor
system” (p. 12).
39 Dr. Michael Cima at MIT is one researcher examining in vivo drug
release from implantable MEMS arrays. He is one of the authors on G.
Voskerician et al. 2002. “Biocompatibility and biofouling of MEMS
drug delivery devices.” Biomaterials. 24: 1959–1967.
40 According to Wise, one reason for relatively slow advances over the
past thirty years is because of the “aggressive saltwater environment”
of living tissue. (Quoted in D. Lammers. “Micro medical devices
could transform health care.” EE Times, June 21, 2002; www.eetimes.com/at/news/OEG20020620S0060.)
See also the discussion of Wise’s work in J. DeGaspari. “Tiny,
tuned, and unattached.” Mechanical Engineering, July 1, 2001;
41 “A team of scientists from Japan have developed tiny spinning
screws that can swim along veins. The screws could then be used to ferry
drugs to infected tissues or even burrow into tumours to kill them off
with a hot lance.” “‘Microbots’ hunt down disease.”
BBC News, June 13, 2001; http://news.bbc.co.uk/1/hi/health/1386440.stm.
The micromachines are based on cylindrical magnets. (K. Ishiyama, M.
Sendoh, and K. I. Arai. 2002. “Magnetic micromachines for medical
applications.” J Magnetism Magnetic Materials. 242–245(P1):
42 See the Sandia National Laboratories August 15, 2001, press release
“Pac-Man-like microstructure interacts with red blood cells,”
www.sandia.gov/media/NewsRel/NR2001/gobbler.htm. For an industry trade
article in response, see D. Wilson. “Microteeth have a big bite.”
August 17, 2001; www.
43 P. Ball. “Chemists build body fluid battery.” Nature
Science Update, November 12, 2002; www.
44 M. Bernstein. “Tiny nanowire could be next big diagnostic tool
for doctors.” EurekAlert, December 16, 2003; www.eurekalert.org/pub_releases/2003-12/acs-nc121603.php.
45 J. Sliwa. Researchers envision intelligent implants.” EurekAlert,
July 8, 2003; www.eurekalert.org/pub_releases/2003-07/asfm-rei070303.php.
46 J. Whitfield. “Lasers operate inside single cells,” Nature
Science Update, October 6, 2003; www.
47 Ron Weiss’s home page at Princeton University (www.ee.princeton.edu/~rweiss/)
lists his publications, such as 2003. “Genetic circuit building
blocks for cellular computation, communications, and signal processing.”
Natural Computing, an International Journal. (2): 47–84.
48 S. L. Garfinkel. “Biological computing.” Technology Review,
May/June 2000; www.simson.net/
49 Ibid. See also the list of current research on the MIT Media Lab
Web site; www.media.mit.edu/
1 Great Smokies Diagnostic Laboratory. “Integrative Medicine,”
2 Terry Grossman’s personal experience is by no means unique.
In a recent article in JAMA, the official journal of the American Medical
Association, 46.3 percent of American people consulted a practitioner
of alternative medicine in 1997. (D. M. Eisenberg et al. “Trends
in alternative medicine use in the United States, 1990–1997: results
of a follow-up national survey.” 1998. JAMA. Nov 11;280(18): 1569–75.)
3 N. M. Bressler et al. 2003. “Potential public health impact
of Age-Related Eye Disease Study results: AREDS report no. 11.”
Arch Ophthalmol. Nov;121(11): 1621–1624.
4 Approximately 70 percent of Terry Grossman’s macular-degeneration
patients have experienced some degree of visual improvement with his
treatment protocol, which also includes electrical stimulation of the
eyes, while 25 percent stabilized their existing vision. See also E.
L. Paul. 2002. “The Treatment of Retinal Diseases with Micro Current
Stimulation and Nutritional Supplementation.” Presentation to
the International Society for Low-Vision Research and Rehabilitation
(ISLRR), Göteborg University, Faculty of Medicine, Göteborg,
Sweden; and also L. D. Michael and M. J. Allen. 1993. “Nutritional
Supplementation, Electrical Stimulation and Age-Related Macular Degeneration.”
J Orthomol Med. 8: 168–171.
5 For further information on the nutritional treatment of autistic disorders,
see the DAN! (Defeat Autism Now!) protocols, available through the Autism
Research Institute; www.autism.com/ari/
1 Charles Darwin recognized that one of the primary factors in the size
of an animal population is food, which all species require to survive.
Species are linked in food chains, starting with producers, which create
their own food by converting inorganic compounds into organic compounds.
When plants (producers) create organic compounds through photosynthesis,
they are storing energy that will then be passed up the food chain as
those plants are eaten and then the eaters of those plants are eaten,
and so on. Decomposers break down the complex organic compounds created
by energy conversion and return the nutrients to the soil, where producers
use them once again.
2 Plant cultivation began much sooner than originally thought: there
are signs that squash was cultivated in Ecuador and rice in China 10,000
to 11,000 years ago (H. Pringle. 1998. “Neolithic agriculture:
the slow birth of agriculture.” Science. 282(5393): 1446–1449).
Since then, humans have spread into almost every ecosystem on earth,
eating widely ranging diets. Until recently, the maintenance energy
required to acquire food was a high proportion of all humans’
energy budgets. One reason may be our brains, which require 20 to 25
percent of our energy needs, compared with 8 to 10 percent for nonhuman
primates and 3 to 5 percent for other mammals. Animals with larger brains
typically seek richer diets (W. Leonard. 2002. “Food for thought:
dietary change was a driving force in human evolution.” Sci Am.
Nov 13: 106–115).
Many researchers see a link between obesity in developed countries and
the amount of energy that humans have, until recently, spent on food
acquisition. “It’s only been maybe the last 30 years, certainly
after the Industrial Revolution, since food stopped being scarce,”
says Ann Kelley, a neuroscientist at the University of Wisconsin at
Madison. “No way have the brain and the physiological systems
that regulate body weight had a chance to catch up.” (C. T. Hall.
“Caveman history blamed for U.S. obesity.” San Francisco
Chronicle, January 12, 2003.)
3 According to the U.S. Department of Agriculture (“A history
of American agriculture 1776–1990,” www.usda.gov/history2/text3.htm),
in 1790, farmers made up 90 percent of the labor force in a population
of almost 4 million. By 1840, that percentage dropped to 69 percent.
By 1900, out of a population of 76 million, 38 percent of the labor
force worked on farms, which averaged 147 acres in size. By 1990, only
2.6 percent of the labor force worked on farms, which averaged 460 acres
in size, out of a total U.S. population of 246 million.
4 In 2000, the Centers for Disease Control (CDC) defined poor nutrition
and lack of exercise as the second leading “actual” cause
of death in the United States, behind tobacco. “Actual causes
of death are defined as lifestyle and behavioral factors such as smoking
and physical inactivity that contribute to this nation’s leading
killers including heart disease, cancer and stroke” (“Physical
Inactivity and Poor Nutrition Catching up to Tobacco as Actual Cause
of Death.” March 9, 2004; www.cdc.gov/od/oc/media/pressrel/fs040309.htm).
In that same year, “fewer than one-fourth of U.S. adults reported
eating recommended amounts of fruits and vegetables daily.” (“Chronic
disease prevention: the burden of chronic diseases and their risk factors.”
National Center for Chronic Disease Prevention and Health Promotion;
5 The producers at the bottom of a food chain build complex energy-rich
compounds from four atoms (carbon, nitrogen, oxygen, and hydrogen).
For example, proteins are chains of amino acids, each of which contains
an amino group (NH2) and a carboxyl group (COOH). Proteins are broken
down into their amino acids during digestion, and these amino acids
pass into your bloodstream, from which they are absorbed by cells. Your
body uses 20 out of the approximately 100 amino acids in nature as building
Plants also produce carbohydrates, which your cells absorb and convert
into energy to drive all your bodily functions. Glucose, composed of
six carbon atoms and six water molecules, is one of the simplest carbohydrates
so it can pass directly into the bloodstream. More complex carbohydrates,
made up of chains of glucose molecules, need to be broken down into
glucose molecules before they can be absorbed. Hydrolysis is the enzymatic
reaction that breaks chemical bonds in food through the addition of
6 “The apparent simplicity of the water molecule belies the enormous
complexity of its interactions with other molecules, including other
water molecules” (A. Soper. 2002. “Water and ice.”
Science. 297: 1288–1289). There is much that is still up for debate,
as shown by the numerous articles still being published about this most
basic of molecules, H2O. For example, D. Klug. 2001. “Glassy water.”
Science. 294: 2305–2306; P. Geissler et al. 2001. “Autoionization
in liquid water.” Science 291(5511): 2121–2124; J. K. Gregory
et al. 1997. “The water dipole moment in water clusters.”
Science. 275: 814–817; K. Liu et al. 1996. “Water clusters.”
Science. 271: 929–933.
A water molecule has slightly negative and slightly positive ends, which
means water molecules interact with other water molecules to form networks.
The partially positive hydrogen atom on one molecule is attracted to
the partially negative oxygen on a neighboring molecule (hydrogen bonding).
Three-dimensional hexamers involving six molecules are thought to be
particularly stable, though none of these clusters lasts longer than
a few picoseconds.
The polarity of water results in a number of anomalous properties. One
of the best known is that the solid phase (ice) is less dense than the
liquid phase. This is because the volume of water varies with the temperature,
and the volume increases by about 9 percent on freezing. Due to hydrogen
bonding, water also has a higher-than-expected boiling point.
7 M. S. Jhon. 1989. “Water and health.” Korea Applied Science
Research Center for Water, Seoul, Korea. Other articles include M. S.
Jhon and J. D. Andrade. 1973. “Water and hydrogels.” J Biomed
Mater Res. Nov;7(6): 509–522; and J. D. Andrade et al. 1973. “Water
as a biomaterial.” Trans. Am Soc. Artif. Intern Organs. 19: 1–7.
8 The following study cites many benefits from an alkalinizing diet.
L. A. Frassetto et al. 1998. “Estimation of net endogenous noncarbonic
acid production in humans from diet potassium and protein contents.”
Am J Clinical Nutrition. 68: 576–83. “Normal adult humans
eating Western diets have chronic, low-grade metabolic acidosis, the
severity of which is determined in part by the net rate of endogenous
noncarbonic acid production (NEAP), which varies with diet. . . . Normal
adult humans eating typical American diets characteristically have chronic,
low-grade metabolic acidosis. . . . With advancing age, the severity
of diet-dependent acidosis increases independently of diet. That occurs
because kidney function ordinarily declines substantially with age,
resulting in a condition similar to that of chronic renal insufficiency.
Renal insufficiency induces metabolic acidosis by reducing conservation
of filtered bicarbonate and excretion of acid. Failure to recognize
the respective and independent roles of age-related impaired renal acid-base
regulatory capacity and diet net acid load has until recently prevented
the recognition that low-grade metabolic acidosis is characteristically
present and worsens with age in otherwise healthy adults. . . . Potassium
bicarbonate is a natural base that the body generates from the metabolism
of organic acid salts of potassium (e.g. potassium citrate) (8), whose
density (i.e., mmol K/kJ food item) is greatest in fruit and vegetables.
Long-term supplementation of the diet with potassium bicarbonate has
numerous anabolic effects. In postmenopausal women, for example, calcium
and phosphorus balances improve (1), bone resorption markers decrease
(1), bone formation markers increase (1), nitrogen balance improves
(9), and serum growth hormone concentrations increase (10). These findings
suggest that the adverse effects of chronic, low-grade, diet-dependent
acidosis are not inconsequential and may contribute to such age-related
disturbances as bone mass decline, osteoporosis, and muscle wasting.
One way to reduce or eliminate diet-dependent metabolic acidosis is
by eating diets that impose little or no net acid load.”
9 The body maintains the pH of blood at around 7.4. pH. The pH measure,
first used by the Danish biochemist S. P. L. Sorensen (1868–1939),
expresses the concentration of the hydrogen ion as a number between
1 and 14. A solution with a pH less than 7 is considered acidic, while
a solution with a pH of 7 is considered basic, or alkaline. Thus, human
blood is slightly alkaline.
“The concentration of H+ in blood plasma and various other body
solutions is among the most tightly regulated variables in human physiology.
. . . Acute changes in blood pH induce powerful regulatory effects at
the level of the cell, organ, and organism” (J. Kellum. 2000.
“Determinants of blood pH in health and disease.” Crit.
Care. 4: 6–14). In other words, if the pH level changes by even
a few tenths of a pH unit, serious problems can result.
Disturbances in the acid-base balance in the blood can cause either
acidosis (too much acid, resulting in a decrease in blood pH) or alkalosis
(too much base, resulting in an increase in blood pH). There is still
much debate regarding how to treat the metabolic disorders that cause
these imbalances (see, for example, M. A. Shafiee et al. 2002. “A
conceptual approach to the patient with metabolic acidosis.” Nephron.
92 Suppl 1: 46–55).
10 CH3COOH. Acetic acid, one of the carboxylic acids, is a metabolic
intermediate in the body. Vinegar is a dilute solution of acetic acid
produced by fermenting and oxidizing carbohydrates. See, for example,
S. Weinhouse. 1995. “The acetyl group in fatty acid metabolism.”
FASEB J. Jun;9(9): 820–821; L. R. Empey et al. 1991. “Fish
oil-enriched diet is mucosal protective against acetic acid-induced
colitis in rats.” Can J Physiol Pharmacol. Apr;69(4): 480–487.
11 CH3CHOHCOOH. Lactic acid, one of the carboxylic acids, is found in
the blood as a salt (lactate). The body creates lactic acid by exercising
muscles. This acid is also found in fermented milk products such as
sour milk, cheese, and buttermilk. Certain bacteria create lactates
during fermentation. For more information, see J. S. Pringle and A.
M. Jones. 2002. “Maximal lactate steady state, critical power
and EMG during cycling.” Eur J Appl Physiol. Dec;88(3): 214–216;
B. S. Dien et al. 2002. “Fermentation of sugar mixtures using
Escherichia coli catabolite repression mutants engineered for production
of L-lactic acid.” J Ind Microbiol Biotechnol. Nov;29(5): 221–227;
H. Pitkanen et al. 2002. “Serum amino acid responses to three
different exercise sessions in male power athletes.” J Sports
Med Phys Fitness. Dec;42(4): 472–480.
12 H2CO3. The carbonic acid–bicarbonate buffering system helps
maintain blood pH (see note 11 above). Two types of salt created from
carbonic acid are hydrogen carbonate, which contains HCO3-, and carbonates,
which contain CO32-. For more information, see, for example, S. Kimura
et al. 2003. “Enzymatic assay for determination of bicarbonate
ion in plasma using urea amidolyase.” Clin Chim Acta. Feb;328(1–2):
179–184; A. Vesela and J. Wilhelm. 2002. “The role of carbon
dioxide in free radical reactions of the organism.” Physiol Res.
2002;51(4): 335–339; D. A. Bushinsky et al. 2002. “Acute
acidosis-induced alteration in bone bicarbonate and phosphate.”
Am J Physiol Renal Physiol. Nov;283(5): F1091–1097.
13 C5H4N4O3. In the purine group, uric acid is created as the body digests
proteins. As with other acidic by-products of digestion, uric acid must
be excreted at sufficient levels to avoid health problems such as gout.
For more information, see T. Nakamura et al. 2003. “Serum fatty
acid levels, dietary style and coronary heart disease in three neighboring
areas in Japan: the Kumihama study.” Br J. Nutr. Feb;89(2): 267–272;
F. Perez-Ruiz et al. 2002. “Renal underexcretion of uric acid
is present in patients with apparent high urinary uric acid output.”
Arthritis Rheum. Dec 15;47(6): 610–613.
14 CnH2nO2. Fatty acids are components of lipids and composed of chains
of carbon and hydrogen atoms. The carboxyl group (-COOH) at one end
of a fatty acid makes it a carboxylic acid. Single carbon-to-carbon
bonds make the acid saturated, while double and triple bonds make it
unsaturated. Oleic acid is the most common fatty acid; you can find
it in vegetable oils such as olive, palm, and peanut oil. Oleic acid
also makes up 46 percent of human fat. See, for example, M. Nydahl et
al. 2003. “Achievement of dietary fatty acid intakes in long-term
controlled intervention studies: approach and methodology.” Public
Health Nutr. Feb;6(1):31-40; G. R. Hynes et al. 2003. “Effects
of dietary fat type and energy restriction on adipose tissue fatty acid
composition and leptin production in rats.” J Lipid Res. May;44(5):
893–901; S. F. Knutsen et al. 2003. “Comparison of adipose
tissue fatty acids with dietary fatty acids as measured by 24-hour recall
and food frequency questionnaire in black and white adventists.”
Ann Epidemiol. Feb;13(2): 119–127.
15 H3PO4. Phosphoric acid is used in fertilizers, in dental cements,
and in the sugar and textile industries; it is also used in food products
to provide a fruitlike flavoring. Most of the peer-reviewed literature
focuses on the effects of phosphoric acid on tooth enamel (see, for
example, B. Dincer et al. 2002. “Scanning electron microscope
study of the effects of soft drinks on etched and sealed enamel.”
Am J Orthod Dentofacial Orthop. Aug:122(2): 135–141) and on bone
density, particularly in girls. (See, for example, J. Fisher et al.
2001. “Maternal milk consumption predicts the tradeoff between
milk and soft drinks in young girls’ diets.” J Nutr. Feb:131(2):
246–250; F. Carcia-Contreras et al. 2000. “Cola beverage
consumption induces bone mineralization reduction in ovariectomized
rats.” Arch Med Res. Jul–Aug 31(4): 360–365.)
16 NaHCO3. Sodium bicarbonate is often called the most important pH
blood buffer. Typically, the concentration of bicarbonate in the blood
plasma is 25 millimoles per liter. This level is called the bicarbonate
threshold. The body produces sodium bicarbonate from the carbon dioxide
(CO2) formed in the cells as a by-product of chemical reactions.
After the carbon dioxide filters into the capillaries, it combines with
an enzyme of red blood cells called carbonic anhydrase to form carbonic
acid (H2CO3). This acid quickly separates into hydrogen ions (H+) and
bicarbonate ions (HC3-). The reaction can also reverse, yielding carbon
dioxide and water from bicarbonate and hydrogen ions, with the carbon
dioxide eliminated through the lungs.
Sodium bicarbonate is used as a medicine to relieve heartburn, sour
stomach, or acid indigestion by neutralizing excess stomach acid.
17 Na2HPO4. Sodium phosphate is an important nonbicarbonate base in
the renal system. Monobasic phosphate (NaH2PO4) forms when this base
accepts hydrogen ions.
18 The balance of bases to hydrogen ions is key to how the renal system
eliminates wastes from the metabolism of our food. The kidneys regulate
the blood by filtering 20 percent of the plasma and noncell elements
from the blood, reabsorbing key components (fluid, ions, small molecules)
as needed, and secreting unwanted components in the urine. The entire
blood volume of an adult is typically filtered 20 to 25 times a day.
Bicarbonate is one of the components filtered from the blood and then
reabsorbed. When the concentration of bicarbonate falls below the threshold
of 25 millimoles per liter, no bicarbonate is excreted, which means
all of it is reabsorbed into the blood. When the concentration is higher
than the threshold, bicarbonate is passed into the urine.
19 H2SO4. Sulfuric acid is a strong acid that ionizes to form hydronium
ions (H3O+) and hydrogen sulfate ions (HSO4–). See, for example,
T. Ubuka. 2002. “Assay methods and biological roles of labile
sulfur in animal tissues.” J Chromatogr B Analyt Technol Biomed
Life Sci. Dec 5;781(1-2): 227–249.
20 H3PO4. See note 15 on page 387 on H3PO4 for more detail.
21 The kidneys are an effective mechanism for maintaining the blood
pH. To control the concentration of hydrogen ions, for example, the
kidneys can excrete 2,500 times more ions in the urine than are found
in the blood. Likewise, the kidneys can excrete more or less bicarbonate.
The human body, however, creates many organic and inorganic acids as
it breaks down food; and the more acidic the diet, the more time it
takes for the kidneys to restore the pH balance in the blood. When you
eat an acidic diet, the bicarbonate concentration in the blood is reduced
(as is the pH). The kidneys compensate by secreting more hydrogen ions
in the urine and secreting more bicarbonate back to the blood than it
filtered out. This process continues until the concentrations of hydrogen
and bicarbonate ions
are returned to normal. For more detail, see C. Freudenrich. “How
your kidneys work” (http://science.
Western diets rich in meats and other acid sources, such as colas, produce
a heavy acid load. An increasing level of attention is being paid to
the resulting health effects. See, for example, M. Maurer et al. 2003.
“Neutralization of Western diet inhibits bone resorption independently
of K intake and reduces cortisol secretion in humans.” Am J Physiol
Renal Physiol. Jan;284(1): F32–40; U. S. Barzel. 1995. “The
skeleton as an ion exchange system: implications for the role of acid-base
imbalance in the genesis of osteoporosis.” J Bone Miner Res. Oct;10(10):
1431–1436; L. A. Frassetto et al. 2001. “Diet, evolution
and aging—the pathophysiologic effects of the post-agricultural
inversion of the potassium-to-sodium and base-to-
chloride ratios in the human diet.” Eur J Nutr. Oct;40(5): 200–213.
22 J. Shuster et al. 1992. “Soft drink consumption and urinary
stone recurrence: a randomized prevention trial.” Journal Clinical
Epidemiology, Aug;45(8): 911–6. This study demonstrated a significant
increase in the risk of stone formation for those who consumed phosophoric
acid (found in colas): “those who reported at the time of the
index stone that their most consumed drink was acidified by phosphoric
acid but not citric acid, the experimental group had a 15 percent higher
3 yr recurrence-free rate than the controls, p 5 0.002.” For those
who consumed primarily citric acid, no increase was found in risk.
Similar results were found in J. Shuster et al. 1985. “Primary
liquid intake and urinary stone disease.” Journal Chronic Disease.
38(11): 907–14. “This investigation indicates that there
are important associations between urinary stone disease and a person’s
primary liquid intake. . . . an important (p less than 0.01) positive
association was found between urinary stone disease and soda (carbonated
beverage) consumption. . . . no important associations exist between
urinary stone disease and any of milk, water, or tea, when these beverages
represent a person’s primary liquid intake. Moreover, soda can
be viewed almost synonymously as sugared cola, since few subjects had
diet sodas or sugared non-cola soda as primary fluid.”
The following study concludes with a warning to avoid cola consumption:
A. Rodgers. 1999. “Effect of cola consumption on urinary biochemical
and physiocochemical risk factors associated with calcium oxalate urolithiasis.”
Urology Research. 27(1): 77–81. “Since stone formers are
advised to increase their intake of fluid, the present study was undertaken
to determine the effect of cola beverage consumption on calcium oxalate
kidney stone risk factors. . . . Several risk factors changed unfavourably
following consumption of cola. In males, oxalate excretion, the Tiselius
risk index and modified activity product increased significantly (P
, 0.05). In females, oxalate excretion increased significantly while
magnesium excretion and pH decreased significantly (P , 0.05). Scanning
electron microscopy showed that urines obtained from both sexes after
cola consumption supported calcium oxalate crystallization to a greater
extent than the control urines. It is concluded that consumption of
cola causes unfavourable changes in the risk factors associated with
calcium oxalate stone formation and that therefore patients should possibly
avoid this soft drink in their efforts to increase their fluid intake.”
The following study demonstrated benefit in avoiding urinary stones
from a high fluid intake. R. Siener and A. Hesse. 2003. “Fluid
intake and epidemiology or utolithiasis.” Eur J Clin Nutr, Dec;57
Suppl 2: S47–51. “A review of the literature shows that
an increased urine volume achieved by a high fluid intake exerts an
efficacious preventive effective on the onset and recurrence of urinary
stones.” The following study demonstrated the value of consumption
of alkalinizing mineral water: T. Kessler and A. Hesse. 2000. “Cross-over
study of the influence of bicarbonate-rich mineral water on urinary
composition in comparison with sodium potassium citrate in healthy male
subjects.” Br J Nutr. 84(6): 865–87. “The aim of the
present study on healthy male subjects aged 23–38 years was to
evaluate the influence of bicarbonate-rich mineral water (1715 mg bicarbonate/l)
on urinary-stone risk factors in comparison with sodium potassium citrate,
a well-established treatment in that case. The results showed that the
effect of the bicarbonate-rich mineral water was similar to that of
the sodium potassium citrate, which suggests that it could be useful
in the prevention of the recurrence of calcium oxalate and uric acid
The following study concludes that people with a history of calcium-containing
kidney stones should not avoid calcium and should drink adequate liquids:
G. C. Curhan and S. G. Curhan. 1994. “Dietary factors and kidney
stone formation.” Compr. Ther. 20(9): 485–9. “Specifically,
for individuals who have a history of a calcium-containing kidney stone,
important dietary recommendations should include the following: Achieve
adequate fluid intake to produce at least 2 liters of urine per day.
Avoid calcium restriction (except in the rare instances of excessive
intake of greater than several grams per day). A dietary intake of elemental
calcium of at least 800 mg/day (the current RDA for adults) is recommended
to prevent a negative calcium balance, bone mineral loss, and increased
intestinal absorption of oxalate. At present, there is no evidence to
support the belief that calcium restriction is beneficial and current
data suggest that it may in fact be harmful.”
See also P. M. Hall. 2002. “Preventing kidney stones: calcium
restriction not warranted.” Cleve Clin J Med. Nov;69(11): 885–888;
B. Shekarraiz and M. L. Stoller. 2002. “Uric acid nephrolithiasis:
current concepts and controversies.” J Urol. Oct;168(4 Pt 1):
1307–1314; S. T. Reddy et al. 2002. “Effect of low-carbohydrate
high-protein diets on acid-base balance, stone-forming propensity, and
calcium metabolism.” Am J Kidney Dis. Aug;40(2): 265–274;
N. A. Breslau et al. 1988. “Relationship of animal protein-rich
diet to kidney stone formation and calcium metabolism.” J Clin
Endocrinol Metab. Jan;66(1): 140–146; F. Grases et al. 1998. “Biopathological
crystallization: a general view about the mechanisms of renal stone
formation.” Adv Colloid Interface Sci. Feb;74: 169–194;
J. M. Aguado and J. M. Morales. 1993. “The pathogenesis and treatment
of kidney stones.” N Engl J Med. Feb 11;328(6): 444.
23 NIH. “Kidney Stones in Adults.” http://kidney.niddk.nih.gov/kudiseases/pubs/stonesadults/
24 V. Radosavljevic, S. Jankovic, J. Marinkovic, and M. Djokic. 2003.
“Fluid intake and bladder cancer. A case control study.”
Neoplasma. 50(3): 234–8. The study states, “Multivariate
logistic regression model showed consumption of: soda (OR58.32; 95%CI53.18-21.76),
coffee (OR51.46; 95%CI51.05-2.01) and spirits (OR51.15; 95%CI51.04-1.28)
as statistically significant risk factors, while mineral water (OR50.52;
95%CI50.34-0.79), skim milk (OR50.38; 95%CI50.16-0.91), yogurt (OR50.34;
95%CI50.12-0.97) and frequency of daily urination (OR50.27; 95%CI50.18-0.41)
were statistically significant protective variables. In our study no
statistically significant association was observed for total fluid intake.
The findings suggest consumption of soda, coffee and spirits were indicated
as risk factors for bladder cancer, while mineral water, skim milk,
yogurt and frequency of urination as protective factors for bladder
25 That is the conclusion of G. R. Fernando, R. M. Martha, and R. Evangelina.
1999. “Consumption of soft drinks with phosphoric acid as a risk
factor for the development of hypocalcemia in postmenopausal women.”
Journal Clin Epidemiol. Oct;52(10): 1007–10. “The objective
of this study was to determine the relationship between the consumption
of phosphoric acid-containing soft drinks and hypocalcemia in postmenopausal
women . . . In the multivariate regression analysis consumption of one
or more bottles per day of cola soft drinks showed association with
hypocalcemia (1.28, CI 95% 1.06-1.53). The consumption of soft drinks
with phosphoric acid should be considered as an independent risk factor
for hypocalcemia in postmenopausal women.”
The following study compared diets with primarily “acid precursors”
to diets with primarily “base precursors” and concluded
that diets that promote an alkaline body environment reduce “the
rate of bone loss and the risk of fracture in postmenopausal women.”
D. E. Sellmeyer et al. 2001. “A high ratio of dietary animal to
vegetable protein increases the rate of bone loss and the risk of fracture
in postmenopausal women.” Am J Clin Nutr. Jan;73(1): 118–122.
“Different sources of dietary protein may have different effects
on bone metabolism. Animal foods provide predominantly acid precursors,
whereas protein in vegetable foods is accompanied by base precursors
not found in animal foods. Imbalance between dietary acid and base precursors
leads to a chronic net dietary acid load that may have adverse consequences
on bone. . . . Elderly women with a high dietary ratio of animal to
vegetable protein intake have more rapid femoral neck bone loss and
a greater risk of hip fracture than do those with a low ratio. This
suggests that an increase in vegetable protein intake and a decrease
in animal protein intake may decrease bone loss and the risk of hip
26 M. Bertoni et al. 2002 “Effects of a bicarbonate-alkaline mineral
water on gastric functions and functional dyspepsia: a preclinical and
clinical study.” Pharmacol Res. Dec;46(6): 525–31. “The
present study was performed in order to evaluate: (1) the influence
of a bicarbonate-alkaline mineral water (Uliveto) on digestive symptoms
in patients with functional dyspepsia; (2) the effects of Uliveto on
preclinical models of gastric functions. . . . These findings indicate
that a regular intake of Uliveto favors an improvement of dyspeptic
symptoms.” The preclinical study suggests that the clinical actions
of Uliveto water depend mainly on its ability to enhance gastric motor
and secretory functions.
27 L. A. Frassetto et al., ibid. See note 8 on page 386.
28 Water can dissociate into hydroxide (OH-) ions, which makes it alkaline
(basic), and hydrogen ions (H+). As a result, water can act as a base
or an acid. Drinking alkaline water has been claimed to help with constipation,
diarrhea, high or low blood pressure, and diabetes.
29 C. L. Wabner and C. Y. Pak. 1993. “Effect of orange juice consumption
on urinary stone risk factors.” Journal Urology. Jun;149(6): 1405–8.
The study demonstrates the alkalinizing effect of orange juice: “Compared
to potassium citrate, orange juice delivered an equivalent alkali load
and caused a similar increase in urinary pH (6.48 versus 6.75 from 5.71)
and urinary citrate (952 versus 944 from 571 mg. per day).” The
study concludes that orange juice reduces two underlying processes in
urinary stone formation: “Overall, orange juice should be beneficial
in the control of calcareous and uric acid nephrolithiasis.”
A similar protective effect was found for grapefruit juice and apple
juice in R. Honow et al. 2003. “Influence of grapefruit, orange,
and apple juice consumption on urinary variables and risk of crystallization.”
Br J Nutrition. Aug;90(2): 295–300. “Alkalizing beverages
are highly effective in preventing the recurrence of calcium oxalate
(Ox), uric acid and cystine lithiasis. The aim of the present study
was to evaluate the influence of grapefruit-juice and apple-juice consumption
on the excretion of urinary variables and the risk of crystallization
in comparison with orange juice. . . . We showed that both grapefruit
juice and apple juice reduce the risk of CaOx stone formation at a magnitude
comparable with the effects obtained from orange juice.”
30 A free radical is a molecule that, in contrast to most molecules,
contains at least one unpaired electron and as a result is usually highly
reactive. A considerable body of literature explores the role of oxygen
free radicals in aging as well as in disease processes such as heart
disease and cancer. According to some theories, mitochondrial DNA is
a major target of free radical attack. See, for example, A. Ishchenko
et al. 2003. “Age-dependent increase of 8-oxoguanine-, hypoxanthine-,
and uracil-DNA glycosylase activities in liver extracts from OXYS rats
with inherited overgeneration of free radicals and Wistar rats.”
Med Sci Monit. Jan;9(1): BR16–24; Y. Okatani et al. 2003. “Acutely
administred melatonin restores hepatic mitochondrial physiology in old
mice.” Int J Biochem Cell Biol. Mar;35(3): 367–375; J. Sastre.
2002. “Ginkgo biloba extract EGb 761 protects against mitochondrial
aging in the brain and in the liver.” Cell Mol Biol. Sep;48(6):
685–692; A. Anantharaju. 2002. “Aging Liver: A review.”
Gerontology. Nov–Dec;48(6): 343–353.
31 H. Valtin. 2004. Upcoming article in Journal of Physiology: Regulatory,
Integrative and Comparative Physiology. See American Physiological Society
press release at www.the-aps.org/press/journal/release8-13-02.htm.
1 Glucose, fructose, and galactose are isomers (molecules with the same
number and types of atoms as another molecule, but with different properties).
The different arrangement of atoms gives these sugars different properties.
2 M. Bloomfield and L. Stephens. 1996. Chemistry and the Living Organism,
6th ed. New York: John Wiley and Sons; W. Tamborlane et al., eds. 1997.
The Yale Guide to Children’s Nutrition. New Haven and London:
Yale University Press.
3 E. Westman. 2002. “Is dietary carbohydrate essential for human
nutrition?” Am J Clin Nutr. 75(5): 951–953. The established
human nutrients are water, energy, amino acids, essential fatty acids,
vitamins, minerals, trace minerals, electrolytes, and ultratrace minerals.
(A. E. Harper. “Defining the essentiality of nutrients.”
In M. D. Shils et al., eds. 1993. Modern Nutrition in Health and Disease,
9th ed. Boston: William and Wilkins, pp. 3–10.)
4 Lactose intolerance varies by age and by race. The activity of the
enzyme lactase declines after babies are weaned, so most of the human
adult population is lactose-intolerant (J. L. Vilotte. 2002. “Lowering
the milk lactose content in vivo.” Reprod Nutr Dev. Mar–Apr
42: 127–132). Depending on race, the deficiency occurs in 50–90
percent of most populations. “White, western Europeans are the
exception.” A. Ferguson. 1995. “Mechanisms in adverse reactions
to food.” Allergy. 50: 32–38.
5 W. Willett and M. Stampfer. 2003. “Rebuilding the food pyramid.”
Sci Amer. Jan: 64–71; “The basics of good nutrition: Essential
nutrients and their functions.” In D. Tapley et al., eds. 1995.
Columbia University College of Physicians and Surgeons Complete Home
Medical Guide. New York: Crown Publishers (or available online at http://cpmcnet.columbia.edu/texts/guide).
6 Our primate ancestors also could not digest fiber (K. Milton. 1993.
“Diet and primate evolution.” Sci Amer. Aug: 86–93).
See also “The basics of good nutrition: Essential nutrients and
their functions.” In D. Tapley et al., eds. 1995. Columbia University
College of Physicians and Surgeons Complete Home Medical Guide. New
York: Crown Publishers (or available online at http://cpmcnet.columbia.edu/texts/guide).
7 Fructose has a glycemic index in the 30s. Glucose and sucrose, along
with white bread and potatoes, have index values over 85. In fact, glucose
is sometimes used as the reference food for the scale, with an index
of 100. For more information, see K. Foster-Powell et al. 2002. “International
table of glycemic index and glycemic load values: 2002.” Am J
Clin Nutr. 76(1): 5–56.
8 Insulin surges lead to overeating and also foster the deposition of
fat. D. S. Ludwig et al. 1999. “High glycemic index foods, overeating,
and obesity.” Pediatrics. Mar;103: E26; D. S. Ludwig. 2001. “Relation
between consumption of sugar-sweetened drinks and childhood obesity:
a prospective, observational analysis.” Lancet. Feb 17;357: 505–508.
This last study found that “each additional sugar-sweetened drink
consumed” per day significantly increased a child’s chance
of developing obesity later.
9 F. S. Facchini et al. 2001. “Insulin resistance as a predictor
of age-related diseases.” J Clin Endocrinol Metab. Aug;86(8):
3574–3578; J. Salmeron et al. 1997. “Dietary fiber, glycemic
load, and risk of non-insulin-dependent diabetes mellitus in women.”
JAMA. Feb 12; 277(6): 472–477.
10 The bulk provided by insoluble fiber increases stool size and shortens
stool transit time through the intestine. Shorter transit times are
better for bowel function. There is less time, for example, for “bad”
bacteria to proliferate and produce toxins. In addition, insoluble fiber
may inhibit the metabolism of carcinogens in the gut. In ascertaining
the contribution of insoluble fiber to preventing colon cancer, it has
been difficult to distinguish between the potential benefits of the
fiber and the benefits of other cancer-inhibiting nutrients found in
fiber-rich foods such as vegetables. S. A. Bingham et al. 2003. “Dietary
fibre in food and protection against colorectal cancer in the European
Prospective Investigation into Cancer and Nutrition (EPIC): an observational
study.” Lancet. May 3;361(9368) :1496–1501; U. Peters et
al. 2003. “Dietary fibre and colorectal adenoma in a colorectal
cancer early detection programme.” Lancet. May 3;361(9368): 1491–1495;
S. Gråsten et al. 2000. “Rye bread improves bowel function
and decreases the concentrations of some compounds that are putative
colon cancer risk markers in middle-aged women and men.” J Nutr.
11 N. M. Avena and B. G. Hoebel. 2003. “Amphetamine-sensitized
rats show sugar-induced hyperactivity (cross-sensitization) and sugar
hyperphagia.” Pharmacol Biochem Behav. Feb;74(3): 635–639;
C. Colantuoni et al. 2002. “Evidence that intermittent, excessive
sugar intake causes endogenous opioid dependence.” Obes Res. Jun;10(6):
478–488; C. Colantuoni et al. 2001. “Excessive sugar intake
alters binding to dopamine and muopioid receptors in the brain.”
Neuroreport. Nov 16;12(16): 3549–3552.
12 C. B. Ebbeling and D. S. Ludwig. 2001. “Treating obesity in
youth: should dietary glycemic load be a consideration?” Adv Pediatr.
48: 179–212; S. B. Roberts. 2000. “High-glycemic index foods,
hunger, and obesity: is there a connection?” Nutr Rev. 58: 163–169.
13 S. Higgenbotham et al. 2004. Dietary glycemic load and risk of colorectal
cancer in the Women’s Health Study. J Natl Cancer Inst. Feb 4;
14 K. Foster-Powell et al. 2002. “International table of glycemic
index and glycemic load values: 2002.” Am J Clin Nutr. Jul;76(1):
15 For more complete lists, see www.lifelonghealth.us/mhc_home/pdf_docs/GLYCEMIC_INDEX.pdf;
C. T. Netzer. 2000. The Complete Book of Food Counts. New York: Dell.
16 These findings were especially pronounced in overweight women. S.
Liu et al. 2001. “Dietary glycemic load assessed by food-frequency
questionnaire in relation to plasma high-density-lipoprotein cholesterol
and fasting plasma triacylglycerols in postmenopausal women.”
Am J Clin Nutr. Mar;73(3): 560–566.
17 G. M. Reaven. 2003. “Age and glucose intolerance.” Diabetes
Care. 26: 539–540; G. M. Reaven. 1998. “Insulin resistance
and human disease: a short history.” Basic Clin Physiol Pharmacol.
9(2–4): 387–406. “The number of adults in the United
States with diabetes increased by 49 percent between 1991 and 2000 .
. . and Type II diabetes accounts for practically all of that increase”
(J. Marx. 2002. “Unraveling the causes of diabetes.” Science.
296(5568): 686–689, summarizing Centers for Disease Control and
18 M. Blüher et al. 2003. “Extended longevity in mice lacking
the insulin receptor in adipose tissue.” Science. Jan 24;299(5606):
572–574; S. H. Golden et al. 2002. “Risk factor groupings
related to insulin resistance and their synergistic effects on subclinical
atherosclerosis: the atherosclerosis risk in communities study.”
Diabetes. Oct;51: 3069–3076; F. Wollesen et al. 2002. “Insulin
resistance and atherosclerosis in diabetes mellitus.” Metabolism.
19 J. Marx. 2002. “Unraveling the causes of diabetes.” Science.
296(5568): 686–689; R. K. Campbell and J. R. White. 2002. “Insulin
therapy in type 2 diabetes.” J Am Pharm Assoc. Jul–Aug;42:
602–611; G. M. Reaven. 1999. “Insulin resistance: a chicken
that has come to roost.” Ann NY Acad Sci. Nov 18;892: 45–57.
20 F. Abbasi et al. 2002. “Relationship between obesity, insulin
resistance, and coronary heart disease risk.” J Am Coll Cardiol.
Sep 4;40(5): 944–945; S. Liu and W. C. Willett. 2002. “Dietary
glycemic load and atherothrombotic risk.” Curr Atheroscler Rep.
Nov 4: 454–461; G. M. Reaven. 2000. “Diet and Syndrome X.”
Curr Atheroscler Rep. Nov;2(6): 503–507; S. Liu et al. 2000. “A
prospective study of dietary glycemic load, carbohydrate intake, and
risk of coronary heart disease in U.S. women.” Am J Clin Nutr.
71(6):1455–1461; J. Yip et al. 1998. “Resistance to insulin-mediated
glucose disposal as a predictor of cardiovascular disease.” J
Clin Endocrinol Metab. Aug;83(8): 2773–2776.
21 High glycemic load has been noted as a risk factor for pancreatic,
breast, and colon cancers. See, for example, D. S. Michaud. 2002. “Dietary
sugar, glycemic load, and pancreatic cancer risk in a prospective study.”
J Natl Cancer Inst. 94(17): 1293–1300; L. S. Augustin et al. 2001.
“Dietary glycemic index and glycemic load, and breast cancer risk:
a case-control study.” Ann Oncol. 12(11): 1533–1538; E.
Giovannucci. 2001. “Insulin, insulin-like growth factors and colon
cancer: a review of the evidence.” J Nutr. Nov;131(11): 3109S–20S.
22 Discovered in 1879, saccharin is 300 times sweeter than sugar. In
1977, when the Food and Drug Administration (FDA) proposed to ban saccharin,
it was the only alternative sweetener. The public outcry prompted Congress
to pass the Saccharin Study and Labeling Act, which required foods containing
saccharin to display a warning label. That requirement remained in place
for more than two decades. Even though the government now claims to
have exonerated saccharine through the Saccharin Warning Elimination
via Environmental Testing Employing Science and Technology Act of 2000,
many scientists remain concerned about the tens of millions of people
consuming the sweetener and evidence of carcinogenesis. See, for example,
W. Bell et al. 2002. “Carcinogenicity of saccharin in laboratory
animals and humans.” Int J Occup Environ Health. Oct–Dec;8:
387–393; Y. Sasaki et al. 2002. “The comet assay with 8
mouse organs: results with 39 currently used food additives.”
Mutation Research. 519(1–2): 103–119.
23 H. J. Roberts. 1992. Aspartame (Nutrasweet): Is It Safe? New York:
The Charles Press. As with saccharin, controversy continues to rage
over the safety of aspartame. The FDA defends the sweetener, although
research shows a variety of possible heath effects (see, for example,
S. K. van den Eeden et al. 1994. “Aspartame ingestion and headaches:
a randomized crossover trial.” Neurology. Oct;44(10): 1787–1793).
24 R. J. Wurtman. 1983. “Neurochemical changes following high-dose
aspartame with dietary carbohydrates.” N Engl J Med. Aug 18;309(7):
429–30; “Migraine provoked by aspartame.” 1986. N
Engl J Med. Aug 14;315(7): 456; S. E. Moller. 1991. “Effect of
aspartame and protein, administered in phenylalanine-equivalent doses,
on plasma neutral amino acids, aspartate, insulin and glucose in man.”
Pharmacol Toxicol. 68(5): 408–412.
25 Soluble fiber can be digested by the body as opposed to insoluble
fiber, which cannot. D. L Sprecher and G. L. Pearce. 2002. “Fiber-multivitamin
combination therapy: a beneficial influence on low-density lipoprotein
and homocysteine.” Metabolism. Sep;51(9): 1166–1170; B.
M. Davy et al. 2002. “High-fiber oat cereal compared with wheat
cereal consumption favorably alters LDL-cholesterol subclass and particle
numbers in middle-aged and older men.” Am J Clin Nutr. Aug;76(2):
Eating soluble fiber may also be beneficial for individuals with syndrome
X. (B. M. Davy and C. L. Melby. 2003. “The effect of fiber-rich
carbohydrates on features of Syndrome X.” J Am Diet Assoc. Jan;103(1):
26 Insoluble fiber cannot be digested by humans and is found in foods
such as wheat bran, vegetables, and whole grains. M. Hill. 2003. “Dietary
fibre and colon cancer: where do we go from here?” Proc Nutr Soc.
Feb;62(1): 63–65; American Dietetic Association and Dietitians
of Canada. 2003. “Position of the American Dietetic Association
and Dieticians of Canada: Vegetarian Diets.” Can J Diet Pract
Res. Summer;64(2): 62–81.
27 A. Mukherjee and J. Chakrabarti. 1997. “In vivo cytogenetic
studies on mice exposed to acesulfame-K-a non-nutritive sweetener.”
Food Chem. Toxicol. Dec;35(12): 1177–1179.
28 See www.ffcr.or.jp/zaidan/FFCRHOME.nsf/pages/e-kousei-sucra for Japanese
studies on the safety of sucralose.
29 Stevia is a Paraguayan plant. Each leaf of stevia “contains
9 to 13 percent stevioside, which is 300 times sweeter than sugar.”
Stevia has been used as a sweetener in Japan for over three decades;
this may be a reason for the number of Japanese studies on the plant.
(See, for example, E. Koyama et al. 2003. “In vitro metabolism
of the glycosidic sweeteners, stevia mixture and enzymatically modified
stevia in human intestinal microflora.” Food and Chem Toxicol.
41(3): 359–374; M. Matsui et al. 1996. “Evaluation of the
genotoxicity of stevioside and steviol using six in vitro and one in
vivo mutagenicity assays.” Mutagenesis. Nov;11(6): 573–579.)
Voyage: Live Long Enough to Live Forever by Ray Kurzweil and Terry
Grossman M.D. Rodale: 11/2004 ISBN#1-57954-954-3