The Evolution of Personalized Nutrition—From Addis, Pauling, and RJ Williams to the Future

Abstract

As forward progress continues, coupling together a person’s genomic and epigenomic patterns with the deciphering of information that resides within the noncoding or “dark matter” of the human genome will revolutionize all fields of health care and certainly medical nutrition therapy. The more information we obtain in this field, the more we recognize that nutritional needs are not determined by single SNPs alone. Rather, it is more accurate to say that families of genes function together in a network to regulate metabolic function and its relationship to specific nutrients. The days of one-size-fits-all thinking about dietary recommendations are being replaced by excitement about specific genomic and biometric-based personalized recommendations.

Linus Pauling, PhD, (1901-1994) was one of only four people in history to be the recipient of two Nobel Prizes. His fellow double honorees include Marie Curie, John Bardeen, and Frederick Sanger, but because he independently received his first prize in Chemistry (1954) and his second in Peace (1962), Dr Pauling was—and continues to be—the only person to have been awarded two unshared Nobel Prizes in two different fields. Dr Pauling had both a long and celebrated career and a long and celebrated life and he is remembered by different people for different reasons. Some consider him to be one of the greatest chemists to live in the modern era, while others think of him as a champion for peace because of his commitment to nuclear disarmament. Clinicians and scientists often think of his work in medicine on the concept of molecular disease, and for other people it is his study of nutrition that stands out. As a result of Dr Pauling’s intense interest in vitamin C that culminated with the publication of his book Vitamin C and the Common Cold in 1970, many people credit him with being the father of the dietary supplement industry.¹

How does a retrospective look at the work of the legendary Dr Linus Pauling relate to the present explosion in interest in personalized nutrition and the development of this field in the 21st century? I passionately feel that our past can always inform our future. In the early 1980s, I spent 2 years working as a research associate at the Linus Pauling Institute of Science and Medicine while on sabbatical from my teaching position as a chemistry professor at the University of Puget Sound in Tacoma, Washington. What a tremendous privilege it was to have an office located just down the hall from such a great man. Our proximity and shared interests led to many conversations that I look back on not only with fondness but with clarity. Through the lens of time and experience, I now recognize how the development of personalized nutrition is reflected in the creative genius of Dr Linus Pauling.

My narrative begins in a car—stuck in traffic—in the fall of 1982. I was at the wheel and Dr Pauling was my passenger, and the two of us were driving from Palo Alto to San Francisco International Airport. It was rush hour, and while we were captive in the car, Dr Pauling recounted a story to me about the time he and his wife, Ava Helen, were at a scientific meeting on the East Coast in the late 1930s. While at that meeting, Dr Pauling took ill with a severe inflammation of his kidneys. He had to travel back to California by train and his condition became increasingly worse during this journey. Thanks to his connections, Dr Pauling was referred to a specialist at Stanford University who was arguably the leading nephrologist of his time, Thomas Addis, Jr, MD. Dr Addis confirmed the diagnosis as glomerulonephritis, also called Bright’s disease, for which he had developed a treatment in the form of a special diet. Since renal dialysis was not developed until 1943, the Addis Diet was the only option available to patients with this condition at the time of Dr Pauling’s episode.

Dr Addis began using dietary therapy to treat Bright’s disease in the early 1920s. His approach took into account not only reducing the load of salts on the kidney, but also the need to find the right balance of protein to reduce excessive urea while maintaining lean body mass. His therapeutic diet was based on a low-calorie, low-salt, low-protein concept, with added vitamin supplementation in light of the restricted food intake. As he worked with patients with Bright’s disease, Dr Addis was able to show that proteinuria increases with increasing levels of dietary protein intake, but without changes in the serum protein concentration. In a later review about the legacy of Dr Thomas Addis, Jr, his considerable success in treating patients with chronic Bright’s disease was summarized in the following way: “[It] may have resulted in part from his realization of the need to individualize dietary therapy in his patients, in order to gain the benefits of a low-protein diet without incurring an excessive risk of protein malnutrition, as well as from the utility of his team approach (doctor-dietician-laboratory staff) in establishing that balance.”² Dr Pauling complied with the dietary program designed by Dr Addis and he felt that doing so saved his life. This experience also led him to recognize the importance of nutrition in metabolic disorders and the value of micronutrients in regulating metabolism. Was Dr Addis the first prominent leader in medical science to advocate personalized nutrition as a treatment for a specific disease? Many people suggest that he should be recognized for this significant contribution to the field.^3,4

Consider, for a moment, the power and impact of a personal experience. Because of his interaction with Dr Addis and the success of his own treatment program, Dr Pauling came to better understand and recognize the biochemical importance of nutrition and the genetic uniqueness of specific nutrients—knowledge that was profoundly important to his discoveries in the field he defined as molecular disease.⁵ Consider, too, serendipitous timing. During the 1940s, Dr Pauling began a collegial correspondence with Roger J Williams, PhD, at the University of Texas, who was the discoverer of pantothenic acid, folic acid, and pyridoxine (vitamin B₆). At the time Dr Pauling was doing some of his most significant work, Dr Williams was simultaneously developing his concepts of the “genetotrophic origin of disease” and “biochemical individuality.”^6-10 Together, Pauling and Williams launched the modern field of personalized nutrition.

Pauling, Williams, and the Dawn of Personalized Nutrition

What is a genetotrophic disease? Dr Williams defined it as a disease that occurs in an individual if the diet fails to provide a sufficient supply of one or more nutrients that are required at higher levels due to unique genetic needs. He felt that many chronic health problems or later-stage disease resulted from the insufficiency of the diet to provide certain individuals with specific nutrients at levels required for optimal physiological function that were determined by genetic uniqueness.¹¹ Health problems linked to personal nutrient insufficiencies could, in many cases, take decades to appear. The personalized nutrition concept was further advanced by Dr Pauling in 1968 when he coined a new term: “orthomolecular” nutrition. This concept focuses on meeting the genetically determined nutrient needs of the individual in optimal concentrations to support the proper structure and function of the body.¹² By 2003, a new era had emerged, and a new generation of researchers was carrying the early work of Pauling and Williams forward. That year, Robert P Heaney, MD, a distinguished professor of medicine at Creighton University, was presented with the EV McCollum Award by the American Society of Nutrition. In his acceptance lecture, Dr Heaney discussed his work on long-latency nutritional deficiency diseases, a field of study that continues to be highly regarded to this day.^11,13

Connecting the Pioneers to Contemporary Research

How did the combined work of Addis, Pauling, and Williams lay the groundwork for the genomic discoveries of the 21st century, some of which have been refined and implemented into clinical practice? For context, let’s return to the work of Linus Pauling. Dr Pauling asserted genetic and evolutionary information should be used to establish personalized nutritional recommendations in support of an individual’s optimal structure and function (as opposed to the amount of a nutrient needed to prevent an immediate deficiency). He used ascorbic acid (vitamin C) and goats to illustrate his point. A goat has about the same body weight as an adult human, but unlike humans, goats make vitamin C in their livers. An adult goat will produce approximately 13 000 mg of vitamin C a day in its liver to support its structure and function. For humans, the recommended daily intake is of vitamin C is 60 mg, which is more than enough to prevent scurvy, a vitamin C deficiency disease, but—as Pauling argued using evolutionary and genetic rationale—far below what might be considered optimal.¹⁴ While humans cannot make their own vitamin C, it has been found that they do recycle the vitamin C consumed in their diets. This allows humans to retain vitamin C longer than animals that produce vitamin C through their own metabolism. Many decades after Pauling’s work, the question as to what the optimal intake of vitamin C is in an individual based on their specific genes, lifestyle, environment, and health status remains unanswered.

Michael Fenech, PhD, is a leading researcher based in Australia. In 2010, Dr Fenech published a set of dietary reference values of individual micronutrients. His lab had collected more than two decades of research data about the genetic sensitivity of nutrients and their relationship to metabolic function and DNA stability.¹⁵ Using this genomic-based approach to the determination of micronutrient need reveals that the reference values for the various nutrients are much higher than the traditional dietary reference values that were established to prevent nutrient-deficiency diseases such as beriberi, scurvy, pellagra, xerophthalmia, and rickets.

Since the decoding of the human genome was announced in the early 2000s, a veritable plethora of genetic variants or single nucleotide polymorphisms (SNPs) have been identified that have some relationship to a person’s specific sensitivities to their lifestyle and diet.¹⁶ These emergent discoveries and the parallel development of new technologies are driving the development of the field of nutrigenomics, which is the science that underpins the evolution of personalized nutrition. As forward progress continues, coupling together a person’s genomic and epigenomic patterns with the deciphering of information that resides within the noncoding or “dark matter” of the human genome will revolutionize all fields of health care and certainly medical nutrition therapy. The more information we obtain in this field, the more we recognize that nutritional needs are not determined by single SNPs alone. Rather, it is more accurate to say that families of genes function together in a network to regulate metabolic function and its relationship to specific nutrients. The days of one-size-fits-all thinking about dietary recommendations are being replaced by excitement about specific genomic and biometric-based personalized recommendations. One example that is backed by science and gaining global attention is the management of blood sugar and insulin using data through biometric and intestinal microbiomic genetic analysis to guide dietary recommendations.¹⁷ This approach has been found to provide more accurate and personal information about an individual’s requirements for blood sugar management than using population-based glycemic index data.¹⁸

Revolutionary research is also taking place in the field of autoimmunity. It is now recognized that the old adage “the food of one person can be the poison of another” really comes to life when examining the influence of potential food-borne antigens on the immune system. The study of gluten sensitivity provides an excellent example of this. Fasano and Leonard, two leading researchers, have published work that describes how gluten in the diet is a risk factor to celiac disease and potentially other systemic autoimmune diseases based upon genomic uniqueness as well as quantity of gluten in the diet.¹⁹

Discoveries are expanding deeper, wider, and farther than anyone might have thought just a few years ago. Genetic risk scores are now being developed by polygenetic analysis that define the potential of unique dietary responses to fat, carbohydrate, and protein in the individual.^20-22 Genomic analysis has also identified categories based on genetic uniqueness that are being called “spendthrift versus thrifty phenotypes.”²³ Those individuals with “spendthrift phenotypes” convert calories to heat much more rapidly than those who have “thrifty phenotypes” that are more likely to store calories as fat. Information of this type could be tremendously helpful to patent management in a clinical setting.

It has also come to be recognized that genetic variation in taste-receptor genes not only influences taste perception and food choices. Of possibly even greater importance is the fact that these receptors may have functions far beyond taste. It has been determined that these receptors also serve as chemoreceptors that translate food messages of sweet, bitter, salty, and sour into hormonal messages in the enteroendocrine system, which includes secretion of GLP-1, ghrelin, PYY, glucagon, gastrointestinal inhibitory peptide, cholecystokinin, oxyntomodulin, resistin, leptin, and sex hormones.²⁴ This taste receptor signaling system has been identified to influence insulin sensitivity, lipid metabolism, and adiposity.²⁵

Forging the Era of Personalized Nutrition and Nutrigenomics

Personalized nutrition is coming of age through advances that are being made in nutrigenetics and nutrigenomics.²⁶ New approaches to the personalization of diets and medical nutrition therapies are being delivered and refined. It is now recognized that food is truly medicine and nutrients have specific biological response-modifying functions that are genetically determined. The evidence for this model can be found in controlled studies such as the Food4Me randomized trial.²⁷ Bioactive nutrients in the diet that can influence physiological function have been found to be genetically linked and the range is far greater than the macro and micronutrients. Literally thousands of phytochemicals found in plant foods are now being studied, including flavonoids, polyphenols, lignans, carotenoids, chalcones, humulones, terpenes and glucosinolates. These phytochemicals have been found to exert influence on genetic expression through signal transduction processes and impact can be influenced by the genetic status of the individual.²⁸ The interrelationship among and between the composition of the diet, the genetics of the individual, and the genetics of the intestinal microbiome have been identified as a biological system that regulates physiological response to diet. Dr Roger J Williams once said the following: “Nutrition is for real people. Statistical humans are of little interest.”²⁹ Decades later, science is demonstrating how very prescient this comment was.

Are we there yet, in this new age of personalized nutrition? My answer is: yes. Nutrigenomics, metabolomics, biometrics, and informatics are being harnessed to create an evidence-based approach to medical nutrition therapy that will be applied to both the prevention and management of chronic degenerative diseases.³⁰ In a relatively short period of time, we have seen the personalized nutrition industry evolve from a dream to a reality. Billions of dollars of investment capital is now making its way into the development of new personalized nutrition companies. Major global food companies such as Nestle Health Science, Danone, and DSM have entered the personalized nutrition business space.³¹ The humble beginnings of personalized diets have morphed into the nutrigenomic, science-based, personalized nutrition of today. These developments will pave the way to the application of personalized nutrition as a fundamental tool in the lexicon of all healthcare providers in the years to come, and this in turn will prompt a transformation of healthcare delivery models to focus on the concept of personalized lifestyle medicine.³²

In the September 24, 2019 issue of the Journal of the American Medical Association, an editorial titled “US Dietary Guidance—Is It Working?” was published. The authors, Lisa Van Horn, PhD, RDN, and Marilyn C Cornelis, PhD, state the following: “The application of advanced biomarker discovery technology and knowledge of genetic and gut microbiota differences in response to diet offer promising new strategies toward optimizing nutrition research while leveraging existing resources. …These methods also encourage enthusiasm for personalized or precision nutrition in contrast with the current population-based model that provides nonspecific healthy eating advice. … [W]ith continued investment in precision nutrition and precision medicine more broadly, future dietary guidelines might incorporate a similar approach; perhaps extending age-specific guidelines to other subgroups defined by certain biological factors.”³³ A very long time ago, Linus Pauling and Roger J Williams saw the future of personalized medicine as a component of precision lifestyle medicine. We are all now witnessing the realization of their vision.

Biography

Jeffrey S. Bland, PhD, FACN, FACB, is the president and founder of the Personalized Lifestyle Medicine Institute in Seattle, Washington. He has been an internationally recognized leader in nutrition medicine for more than 25 years. Dr Bland is the cofounder of the Institute for Functional Medicine (IFM) and is chairman emeritus of IFM’s Board of Directors. He is the author of the 2014 book The Disease Delusion: Conquering the Causes of Chronic Illness for a Healthier, Longer, and Happier Life.