When I started work as Public Health Toxicologist with the California Department of Public Health a little more than fifty years ago, the word “toxic” was seldom heard much less used as a topic of conversation. In recent years, the word has been discovered and become a fashionable adjective for a wide variety of undesirable things.

This has bothered me because ‘toxic’ has a very specific meaning that makes it an unacceptable adjective to use except when applied to harmful chemicals. Its use otherwise only confuses people and needlessly frightens them. I usually ignore the matter, but when specific foods are labeled as toxic, I can no longer remain silent.

The toxicity of chemicals may seem an odd subject for a website devoted to all things ketogenic. However, when one realizes that most things ketogenic are chemicals and that all chemicals obey the natural laws that govern toxicity, the idea of an article on toxicology in Ketopia may not be too far a stretch. To keep the discussion relevant, what makes chemicals toxic (harmful) will be explained using fructose and its imprudent “toxic” label for illustration.

A food, by definition, cannot be toxic. A food is a plant or animal product that is accepted by fact or custom as a substance that sustains life, supplies energy, and provides for growth, repair, and maintenance when taken into the body, usually by mouth. A toxic chemical is defined as a poison, which is a substance that destroys life or impairs health. These two categories are mutually exclusive. Despite the fact that the two are categories are exclusive of each other, they both obey the same natural laws of the science of toxicology.

The most recent nutrient to be tossed into the toxic pile is fructose. There is no argument that fructose is a harmful food when consumed in excessive amounts. What are excessive amounts? That has not yet been established, but the tremendous increase in unanticipated health problems accompanying consumption of high fructose products has alerted nutritional science that something really bad about dietary fructose is afoot.

We know that the metabolic breakdown of fructose bypasses glycolysis and joins the glucose pathway as it forms pyruvate for entry into the Krebs cycle. To this extent, fructose has the same inflammatory outcomes in kind if not in degree as glucose. Because of the structural difference between glucose and fructose, fructose has a very low glycemic index and is invisible to insulin. For these reasons, fructose was once considered to be a good sweetener for use by diabetics. This was the extent of what was known about the biochemistry of fructose when sugar was expensive and availability of fruits was only “in season.”

We have learned in recent years that consumption of large amounts of fructose is associated with high uric acid levels and gout. This was quite a puzzle because biochemists knew there is no way for the body to make uric acid from fructose. Good biochemical detective work revealed that the activation of dietary fructose by the enzyme fructokinase was an extremely energy expensive process that significantly depleted the body’s chemical energy pool.

In brief: The energy pool depletion results in local deficiencies of energy that cause massive numbers of cell deaths; cell death disintegration causes release of genetic material from the dead cells; disposal of genetic material involves breakdown to uric acid; the large amount of uric acid formed overwhelms the ability of kidneys to excrete uric acid, with resulting kidney damage and gout. Serious questions remain. What other more subtle biochemistry is dietary fructose engaging in? What other damage is fructose doing to consumers about which we have yet to learn?

Fructose is a perfect example of a basic tenet of modern toxicology that came from the writings of Paracelsus(1) “What is it that is not poison? All things are poison and nothing is without poison. It is the dose that makes a thing not a poison.” A dose has two parts; “how much” and “how often.” This is true of all chemicals, independent of their source (animal or plant), whether they are natural or synthetic, or what their function is.

The monosaccharide fructose is not known to have any unique role in human biochemistry, but in the small doses of a hundred years ago, it was not known to be harmful. The “how much” was small and the “how often” was infrequent. In fact, fruits were a highly valued food because of the essential micronutrients they contained; the fructose component was not an issue.

Unlike small doses, the large doses of fructose in the modern American diet have been shown to be very harmful. The “how much” is large and the “how often” is frequent. How much fructose consumed in one dose is harmful? How often can an amount of fructose that is thought to be harmless be eaten without eventually causing harm? The answers to these two critical questions are not known, but they must be dealt with to protect the health of the high-carbohydrate consuming public.

The “how much” and “how often” questions about fructose suggest that toxicity is not a simple concept. In fact, the toxicity of chemicals is of two kinds, neither of which actually bears any relationship to the other. Paracelsus was the first to recognize the existence of acute toxicity and chronic toxicity. Acute toxicity refers to the harm done by a chemical as a result of a onetime exposure. Chronic toxicity refers to the harm done by a chemical as a result of many repeated exposures. The Hazardous Substances Labeling Act (HSLA) of 1960 defines categories of toxicity and specifies procedures for toxicity testing.

The acute toxicity of chemicals is not relevant to foods. No substance that produced immediate illness or death from a onetime exposure would ever be considered for use as a food. With regard to chronic harmful effects, such as those now being found with fructose, the methods used for studying chronic toxicity would probably not be precise enough to detect adverse effects in sufficient time to be of value in preventing illness. In any event, the matter of toxicity of foods was resolved by the HSLA. It formalized the long-standing practice of exempting foods from toxicity testing.

There are a few micronutrients that do require exemption from HSLA for use in food because of their toxicity. The one I used often in trying to give people a perspective on “the dose makes the poison,” is actually a poison. That nutrient is vitamin D.

Any chemical that has an LD50 (Lethal Dose for 50 percent of the test animals) of 50 milligrams per kilogram of body weight must carry a Poison label. For a70 kilogram person, 50 milligrams per kilogram is the equivalent of about 1/16th of a teaspoon – a very tiny amount. Pure vitamin D has an LD50 of about 10 milligrams (400,000 International Units) per kilogram; if it were not exempted from HSLA as a food it would have to be labeled as a poison.

Yet vitamin D is an essential nutrient. Humans cannot live without at least 10 micrograms (400 IU) of vitamin D per day(2). This is an eye-opening example for people who think that a chemical that is toxic in any amount is also toxic in every amount. Incidentally, pure vitamin D is not available to the general public, and the vitamin D content in supplements is tremendously diluted.

The exemption of foods from toxicity testing should be of little concern because there are many scientific methods for studying potentially harmful chronic effects of chemicals other than those specified by HSLA. The problems like those of fructose do not come from the foods we have long known, but from new foods that are products of food engineering designed to enhance some commercially valuable quality, such as high fructose corn syrup synthetically concentrated from sugars to enhance their natural sweetness. The blame lays with the food regulatory agencies that permit products of food technology to be classed as foods before adequate investigation justifies their need and safety.

Further, it is criminal for any government agency charged with protecting the health of its people to reject science and support pseudoscience. Official sanction of the unrestricted use of fructose as a substitute for sugar is unacceptable. It is proper to publicize and protest such agency’s malfeasance. But there can be no remedy until someone goes beyond protest and examines the “why” of the malfeasance.

References

  1. Paracelsus was a Swiss physician who lived in the early 1500s. His observations concerning harmfulness or harmlessness of chemicals applies to all chemicals, regardless of their source or use. He is considered the Father of Modern Toxicology.
  2. Frank P, Ottoboni MA. The Dose Makes the Poison: A Plain Language Guide to Toxicology, 3rd Edition. John Wiley & Sons, Hoboken, NJ. 2011