Food for Thought – The Science of Metabolism and Nutrition

On the first day of fall, Sunday, 21 September 2014, the Washington Post’s bestselling non-fiction book list included Blue Ribbon Baking from a Redneck Kitchen and 10-Day Green Smoothie Cleanse: Lose up to 15 Pounds in 10 days – direct evidence of our love-hate relationship with food. The first book offers the red, white and blue of American cooking (white is implicit) to bulk up on beef and the second book offers dietary redemption for the irrational (the only way to lose 15 pounds of useless fat is to cut off your head – which applies especially to diet faddists). The agricultural-industrial revolution that gathered steam in the middle of the last century may have started in 1937, when Jay Hormel created a canned meat product dubbed Spam from ‘shoulder of pork and ham’ that was canned with aspic gelatin; the U.S. Army bought 150 million pounds over the course of World War II. It was certainly in full swing after 1957, when American scientists discovered how to convert cornstarch glucose to fructose to produce a low cost syrup as a food additive. Hominids have been ‘processing’ foods for about 1.8 million years if you consider roasted meat a process, or for about 7,000 years if you consider process as mixing grains and yeast to make bread and beer. [1] The meaning of processed food unalterably changed from combining ingredients and cooking to an admixture of battered grains, mysterious chemicals, and artificial flavors with the advent of mass marketing and industrial scale production of packaged foods. The irony is that while we have mastered titillation of the taste buds, eye-catching packaging, and broadcasting cartoon images like Tony the Tiger proclaiming ‘they’re grrrreat,’ we have almost no clue about what really goes on in our bodies when we drop food down the esophageal hole. There now comes a reckoning. Like lambs to the slaughter, Homo sapiens everywhere queued up for fast food to feed the maw of evolutionary desire for fats and sugars. In the United States, three quarters of all adults are overweight or obese and half are predisposed to diabetes. [2] As the industrial diet spread to the rest of the world, the obesity epidemic spread with it. The World Health Organization estimates that obesity has tripled since 1975 and that 1.9 billion adults are considered overweight and 650 million obese. [3]

Human metabolism is much more complex than food and oxygen in and carbon dioxide and excrement out. Energy extracted to run the body’s plumbing, wiring and locomotion systems must be chemically micromanaged in excruciating detail. What we don’t know is becoming increasingly evident as biology proceeds to unlock the mysteries of how life really works. It took evolution millions of years to work out the details using the inherently messy method of random mutation. One major problem is that people are not lab rats (most of the time); the conduct of scientifically significant human food experiments is nearly impossible. As one example, the USDA did an experiment on humans to determine that the amount of energy extracted from one serving of almonds was 129 calories and not the 170 calories listed on the package label. To arrive at this result, volunteers were instructed to follow their existing diet with the exception of eating more or less almonds and “measuring the unused calories in their feces and urine.” [4] It would be prohibitively expensive and implausible to do this for every food. Testing of hypotheses is thus reduced to analogies between human populations with different diets or using animal surrogates; lab rats again. An experiment at the Scripps Research Institute gave rats a choice between rat food and a smorgasbord of high fat, high sugar foods; almost all chose the latter. As a test of addictive power, the rats were then conditioned to fear a light associated with electric shock and divided into rat food and industrial food groups. When the warning was given, the rat food rats ran and the fast food rats feasted away; the conclusion was that “their hedonistic desire overruled their basic sense of preservation.” [5] Does this mean that obese people are addicted to food? Certainly no one wants to be overly large and many seek guidance to reduce their weight. Fad diets range from the mostly meat paleo/neo-Adkins approach to the traditional lite/low fat regimen of calorie control, mostly to no avail. The recidivism rate for dieters is between 90 and 95 percent. [6] To understand why this is so, it is instructive to look under the hood. At the most basic level, human metabolism is the processing of carbohydrates, fats, and proteins.

Carbohydrates are combinations of sugars (defined as any carbon-hydrogen -oxygen compound with a 1:2:1 ratio). The simplest carbohydrates are monosaccharides (from the Greek word for sugar) with three to seven carbon molecules; glucose and fructose each have six carbons (C6H12O6). Sucrose is composed of one glucose bonded to one fructose; it is the primary end product of photosynthesis, the molecule evolved by plants to be autotrophic or self-feeding. Plants store excess sucrose as starch, a complex carbohydrate or polysaccharide. Carbohydrates are the primary ‘food’ source for plants, animals, and fungi; all species must respire to take in oxygen for the chemical reaction in their cell mitochondria that creates the ionic energy of life. [7] Mammalian sweet sensitivity was an evolutionary adaptation to indicate nutritive plant sugars; bitter meant poison and salt meant minerals. Involution is evolution in reverse, the loss of a trait due to desuetude; carnivore cats gradually lost the sense of sweet and whales only taste salt. [8] Ape-men mostly ate raw leaves and starchy roots in search of sucrose to supplement the occasional successful hunt for animal proteins and fats. Complex carbohydrates were slowly digested as they passed through the stomach and intestines for gradual extraction of glucose to be dissolved in blood for transport. Because cells in critical organs like the heart, lungs, and brain need a continuous supply of glucose, it must be managed; an overdose, called hyperglycemia, is toxic. Insulin is a protein made in the pancreas and dispatched by the brain to regulate glucose concentrations when necessary to stay within limits; it converts excess glucose to the polysaccharide glycogen (the animal equivalent of starch) which is stored in the liver and the muscles and to fat which is stored in fat cells throughout the body. Fructose, the companion of glucose in sucrose, cannot be used directly by the cells and must therefore be either metabolized in the liver or converted to fat and also sent to the blood for distribution to fat cells. [9] It is easy to understand what happens when the industrial diet of processed simple sugars courses through the body. The glucose/fructose tsunami is converted to glycogen and fat; over time the pancreatic insulin is played out with obesity and diabetes as a predictable result.

Carbohydrates became the enemy of the people in the most recent of the food wars that have raged over the last several decades in gut reaction to expanding waistlines. The modern low carbohydrate diet originated with the publication of Dr. Atkins Diet Revolution in 1972, which promoted the substitution of proteins and fats as sugar surrogates. The theory was that the body’s metabolic processes would use more energy if forced to employ gluconeogenesis, the extraction of glucose from either fats or proteins. More recently, this has been taken to the extreme in what are called ketogenic diets, where carbohydrates are reduced to less that 50 grams per day, about 20 percent of the USDA dietary guidelines. The name derives from ketone, a name given to three compounds (acetone, acetoacetate, and hydroxybutyrate) that are produced by oxidation of fatty acids in the liver or kidneys when body metabolism if forced to come up with an alternative to glucose. As this causes acidification of the blood, it is not especially good for you and can be fatal to people with diabetes. [10] While ketogenic diets have been found to reduce weight (so does starvation) when used as a treatment for obesity, “unfortunately, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events.” [11] It is ironic that the low carbohydrate diet was the successor of the 1980’s low fat diet; agribusiness lowered fat and added carbs, mostly fructose sugars, to create highly processed and highly alluring industrial food, the real enemy of the people. Two recent dietary studies put this in perspective; they were seminal in that real people were sequestered in a hospital ward at the National Institutes of Health for the duration so that what they ate was monitored under clinical trial conditions. The first study compared carbohydrate levels and found that “a diet that reduced carb consumption actually seemed to slow the rate of body fat loss.” The second study compared processed food preferences, offering volunteer participants diets of unprocessed and ultra-processed foods with identical calories, carbohydrates, fats, and proteins; they could eat as much of either as they wanted. The result was that people ate an extra 500 calories a day of ultra-processed foods and gained 2 pounds in 2 weeks. [12] While this is not yet settled science, it is a valid data point which makes sense. We should be eating the minimally manipulated foods that our metabolic pathways evolved to eat. So what about fat, a synonym for obese?

Fat is stored energy; emergency backup power when the glucose and glycogen wells have run dry. From the evolutionary perspective, fat is the nutrition repository against starvation; Homo sapiens evolved to store (and crave) fat for a rainy day. Technically, fat is a type of lipid, a mostly hydrocarbon molecule that does not dissolve in water. Because they are hydrophobic, lipids such as cholesterol are the key components of cell membranes; functioning as both barrier and portal for biology’s building block. Most of the body’s fat needs can be met by synthesizing carbohydrates and protein; essential fats in the form of long chain hydrocarbon fatty acids must be consumed from external sources – these are the omega-3 and omega-6 fatty acids that have become the subject of farraginous food advertising. Lipids with fatty acids attached are called glycerides; triglycerides, the main fat storage molecule in both plants and animals, have three. In the food chain, solid triglycerides are called fats and liquids are called oils. It is not altogether clear what essential fatty acids do, but rats fed a diet with absolutely no fat “grew abnormally, their hair fell off, their skin turned scaly, and they died young.” This has not been tried on humans, but it is estimated that we need about one tablespoon a day (rats need less). [13] Since lipids are not water soluble, getting them from one place to another in the blood stream requires a carrier called a lipoprotein. Low density lipoproteins (LDL) carry triglycerides and cholesterol from the liver to the rest of the body and high density lipoproteins (HDL) mostly carry excess cholesterol back to the liver. The LDLs tend to get stuck on artery walls, where they build up over time forming an artery hardening plaque; the chronic condition is called arteriosclerosis and leads to stroke and heart attack. HDL helps remove it, which is why a high ratio of HDL to LDL is an important parameter for healthy blood. Fat cells are distributed throughout the body in specialized cells called adipocytes. As more fat is added, the cells gets larger, literally fattening up. When the body runs out of carbohydrate energy from glucose and glycogen, a hormone called cortisol produced by the adrenal glands triggers the release of triglycerides from fat cells.[14] It is easy to understand what happens when fat is added to a diet already replete with carbohydrates. It has no place to go but to the adipocytes, which grow in size and expand in number to swell the belly that contains them; everything must go somewhere.

Proteins are assembled according to the DNA genetic code from twenty-two different molecules called amino acids. A majority can be metabolized, but nine are essential and must be consumed. The double helix configuration discerned by Francis Crick and James Watson (enabled by the crystallography of Rosalind Franklin) was perhaps the greatest discovery of the 20th century. However, the proposal that the four bases of DNA (adenine, cytosine, guanine and thymine or ACGT) carried the genetic code that was used to make life work required scientific proof to be fact. A series of experiments with bread mold in the 1940’s demonstrated that mutated strains lacked a specific protein enzyme directing a single metabolic function – that there was a direct link between genes and proteins. Some twenty years later, the existence of a genetic code carrier in the form of RNA (using the same bases except uracil U substitutes for T) led to a scientific arms race to fully decipher the code. By 1965, it was shown that each and every amino acid was mapped to a base triplet (e.g. CGT specifies the amino acid Arginine) and that a protein was made from a series of amino acids mapped onto the RNA by a sequence of base pair triplets on the original DNA. In the words of Crick “In the protein molecule, nature has devised an instrument in which an underlying simplicity is used to express great subtlety and versatility.” [15] Proteins from animal or plant sources are necessary for their constituent amino acids that RNA will then reassemble into the proteins that build, repair, and operate every living thing. Proteins are the building blocks of life. Unlike carbohydrates and fats, here nature has the upper hand; the complexity of protein synthesis is not amenable to industrial scale adulteration. There is some legitimate debate about the source of proteins, as cows, pigs and chickens have a large environmental footprint, and some concern about how much red meat the colon can tolerate, but these are inconsequential where the sugar-fat health crisis is concerned.

The average American diet consists of 50 percent carbohydrates (of which 15 percent are simple sugars), 35 percent fats and 15 percent proteins. [16]. USDA dietary guidelines provide the percentage ranges of 45-65 carbohydrates, 20-35 fats and 10-35 proteins, adding proscriptive guidance for daily weights or volumes for vegetables, fruits, grains, dairy, protein food, and oils, and even including caveats to limit added sugars and saturated fats to less than 10 percent of calories. [17] If people followed these rules, the sins of sloth and gluttony would be atoned. But they don’t, and, essentially, they can’t anyway, because the calorie is a really lousy metric for metabolism. The primary measure for food consumed is actually the kilocalorie, the amount of heat needed to raise one kilogram of water one degree centigrade (in common parlance, the thousands prefix ‘kilo’ is dropped). The calorie is one of many measures of the elusive concept energy, that which animates life and defines the atomic age in Einstein’s eternal energy formula. It is a difficult concept – essentially the ability of matter to cause change. Kinetic energy moves and potential energy stores; the rate of using energy is power. From the metabolic perspective of biology, energy is mostly about heat. Thermodynamics is the science of heat necessary for the engineering applications of the 19th century’s industrial revolution steam engines. The Scottish inventor James Watt chose horsepower as the first energy metric to stitch together the new concept with the old. The first quantitative connection between heat and energy was made in 1847 by James Prescott Joule who used a weight of 772 pounds acted on by gravity to turn revolving paddle blades in a tank of water and measured the rise in water temperature. The energy to raise the temperature one degree Fahrenheit for a one foot drop of the weight became the joule, equivalent to about 4.2 calories.[18] This experiment also showed that energy could be converted from one form to another, leading to the seminal First Law of Thermodynamics stating that energy must be conserved; it cannot be destroyed. Metabolism, the thermodynamics of biology, is creating heat energy from food; it is vastly more complex than paddles churning water.

The etymology of calorie is not clear; it was not a unit of heat in the original metric system adopted by post-revolutionary France in 1799 but was officially instituted by the International Metric Convention of 1875. It may have originated from Lavoisier’s use of what he called a calorimeter (from the Latin calor meaning heat) to conduct some of the first experiments on the specific heats of materials. [19] As a wealthy French nobleman endowed with ample resources and leisure time, he indulged in a life of scientific curiosity imbued with keen insight to discover that oxygen, which he named, combined with hydrogen to make water so that mass was conserved, the foundational principle of chemistry which he fathered, his last breath cut short by the guillotine. Lavoisier used his calorimeter to measure the heat produced by a guinea pig, anticipating the work of Wilbur Atwater, an American agricultural chemist who proposed that the calorie could be used to account for both the energy contained in food and the energy expended by metabolic and muscular activity. In the 1890’s he conducted a series of experiments in the basement of Wesleyan University in Connecticut with students who took turns living in a sealed 4×7 chamber with 6 foot walls filled with water for 12 days. By measuring the heat content of the food that they ate using a bomb calorimeter, a device used to burn food to ashes, and the energy they used from the temperature increase of the surrounding water, collecting and burning feces for good measure, he found that one gram of carbohydrates or proteins produced 4 calories and that one gram of fat produced 9 calories. This became the basis for the dietary aphorism that a calorie is a calorie no matter where it comes from and all you need to do is count calories – leading inexorably to the low fat food fad of the late 20th century. [20] In the last twenty years, the complexity of the metabolic process has become clearer as the biological sciences slowly decipher its mysterious codes. For example, proteins may actually need five times more energy to digest than fats due to the difficulty in unwinding their constituent amino acids so they can be reused. The amount of energy the body needs to expend to extract the raw materials from food is a key factor; processed foods are broken down by the energy of industrial machines so that your body doesn’t need to – this is not a good thing. In a 2010 study, people fed a meal of whole grain bread and cheddar cheese used twice as much energy to digest it than a control group that ate the same number of calories comprised of white bread coated with processed cheese product, the poster product of industrial food. The net result was that 10 of the ingested calories in the whole foods group were expended metabolically; those in the processed food group added to their liver glycogen. [21] It is now abundantly clear that calories in is not the same as calories out; the quality of the calorie also counts.

There is also considerable variability between individuals in the utilization of ingested food calories, even though the billions of our species all share the same genome. Uniqueness that is obvious by differences in physiognomy extends by analogy to the metabolic food factory that churns away in the inner sanctum. According to the eminent British dietitian Elsie Widdowson: “Nutritional individuality is a characteristic of mankind, and this is as true of energy intakes and needs as of other attributes. Studies have shown over the years that individuals vary by a factor of two or more in their intakes of energy from the first year of birth to 75 years and over.” [22] Testing of genetically inbred mice fed identical diets and observing differences in weight gain has scientifically confirmed that metabolic process diversification extends to animals in general. Physical differences probably have something to do with it; a study conducted at the turn of the last century for reasons that can only be guessed at (perhaps to answer the proverbial question concerning who was more ‘full of it’) found that one group of Russians had large intestines that were 57 centimeters longer than those of demographically similar Poles. [23] We are also all different in the company we keep; we each have our own personal resident microbiome community. There are trillions of microbes that live, eat and die in our nethermost reaches. While research on its composition and diversity is nascent, it is almost certain to greatly influence individual nutritional profiles; microbes must eat to live, and, so far as we know, they live with us and not on us, to some extent eating what we eat. It has been shown that a high fat and high sugar diet wreaks havoc on the gut microbes of lab animals; the term microbiota-accessible carbohydrate (MAC) has been coined to account for foods that feed the masses. The hunter-gatherer Hadza people of Tanzania have a diet rich in MAC foods and their microbial diversity has been found to be significantly higher than the rest of us subsisting on cultivated crops; they have almost none of the metabolic mismatch diseases that plague modern life. [24] It may be concluded that, while the calorie is a good metric for the amount of heat produced by a random pile of food, it is not particularly useful for metabolic controls – what we refer to as diets. If the calorie is not a good quantitative measure of actual food energy and not a good qualitative way to evaluate food from the metabolic perspective, how can we choose the right food types and quantities for a healthy body and active mind? Since this is the hiker’s notebook, the answer is obvious. Eat rationally and hike as often as you can. Your body and your mind will be forever grateful.

1. Kim, E. “The amazing multimillion-year history of processed food.” Scientific American Volume 309, Number 3 September 2013 pp 50-55.
2. Ludwig, D. et al “Dietary fat: From foe to friend?” Science, Volume 362 Issue 6416, 16 November 2018, pp 764-769.
3. Wan, W. “Global obesity grows more in rural areas, study finds” Washington Post, 9 May 2019.
4. Dunn, R. “Everything you know about calories is wrong” Scientific American Volume 309 Number 3, September 2013, pp 57-59.
5. Kenny, P, “Hooked on Food” Scientific American Volume 309, Number 3, September 2013, pp 46-49.
6. Prologo, D. “Why people regain weight after dieting” Washington Post 9 January 2018
7. Starr, C. and Taggart, R. Biology, The Unity and Diversity of Life 5th Edition, Wadsworth Publishing, Belmont, California, 1989. pp 51-58, 461.
8.McQuaid, J. Tasty Scribner, New York, 2015 p 34
9.Lieberman, D. The Story of the Human Body, Evolution, Health and Disease Pantheon Books, New York, 2013 pp 251-292. A comprehensive overview of mismatch diseases and their importance to the future of human health in the industrial age.
10.Wiliams, S. Nutrition and Diet Therapy, 7th edition, Mosby-Year Book, Inc. Saint Louis, Missouri, 1993, pp. 109-129.
11. Kosinski, C. and Jornayvaz, F. “Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies” Nutrients, Volume 5 Number 9, May 2017 at
12. Shell, E. “Obesity on the Brain” Scientific American, Vol 321, No. 4 October 2019 pp 38-45.
13.Starr, C. and Taggart. R. Op. cit.
14.Lieberman, D. Op. cit.
15.Mukherjee, S. The Gene, Scribner, New York, 2016, pp 139-171.
16.Taubes, G. “Which one will make you fat?” Scientific American Volume 309, Number 3 September 2013 pp 61-65.
18.Whitelaw, I. A Measure of All Things, St. Martin’s Press New York, 2007, pp 123-131.
19.Hargrove, J. “History of the calorie in nutrition” The Journal of Nutrition, Volume 136, Issue 12, December 2006, pp 2957–2961.
20.Wilson, P. “Death of the calorie” 1843, The Economist, April-May 2019, pp 50-59.
21.Dunn, R. “Everything you know about calories is wrong” Scientific American Volume 309, Number 3, September 2013 pp 56-59
22. Widdowson, E. “How Much Food Does Man Require? An Evaluation of Human Energy Needs” in Nutritional Adequacy, Nutrient Availability and Needs, J. Mauron (ed), Springer, Switzerland, 1983, pp 11-25
23. Dunn, R. Op. cit.
24. Gentile, C. and Weir, T, “The gut microbiota at the intersection of diet and human health” Science, Volume 362, Issue 6416, November 2018, pp 776-780.