October 2, 2014

By Dr. Virender Sodhi, ND, MD(Ayurved) and Dr. Anuprao Mulakaluri, ND

In the year 1665, Scientist Robert Hooke was the first person to use the microscope to look at organic tissue. He observed that the tissue was a grouping of small structures; each looked like they were walled off from their surrounding – sort of like the cells of a honeycomb. Hooke called these structures “cells”, a term that is still used to describe the single unit of living tissue. Nearly 350 years later, as our instruments have evolved into transmission electron microscope, our knowledge about the basis of life continues to grow. The discovery of DNA structure is one of the greatest accomplishments of the microscopic studies of the cells. This has developed the science of genomics; which is the study of genes and their effects on our body.

Taking a close look, we find that we have genetic similarity with other humans (99.9% similar), with chimps (98%), with fish (85%), with flies (36%), with plants (>15%).[1] Additionally, the genetic information of all organisms is stored in the same language. This shared genetic language is the Rosetta stone for the similarities of life, and also the basis of diversity across all life forms. Genomic studies have opened our eyes to a deeper understanding genetic individuality among all humans. Genetic understanding has brought us to the modern individualized medicine.

The 0.01% dis-similarity among humans is made of single nucleotide polymorphisms (SNP – pronounced “snips”). SNP’s represents single unit variations within the shared genetic code of people. The effect of these single unit differences or SNP’s trickles up from DNA level to result in variations in the structure of proteins, function and activity of the proteins, composition of cells, activity of the whole organ, and so on; ultimately impacting health of the individual. Knowledge of genomics has directed us towards seeking its application in health-care. There are many applications of genomics that are being developed at this time. Some use genomic information to advance our understanding of constitutional deficiencies, genetic disease, genetic modification of foods, development of vaccines, etc. An emerging application for genomics is to use the genetic information to predict the nutritional needs of the individuals. Nutritional Genomics has finally given western medical sciences a possible tool to begin using food as medicine.

To date, there are almost 1000 human disease genes identified. Most of these are single genes that lead to a specific disease.[2] This knowledge is very useful to understand the disease abnormality and the source of abnormality. For example, the disease called phenylketonuria (PKU) results from a genetic mutation that causes build-up of amino acid phenylalanine. The simple treatment for this disease is to modify the diet to limit the intake of the amino acid phenylalanine.[3] Compared to these single gene diseases, many chronic disease like heart disease, diabetes, Alzheimer’s, multiple sclerosis, etc. involve multiple gene malfunctions. These malfunctions are believed to be due to interaction between the individual genetic information, dietary intake, and the individual’s living environment.

The Evolving Disease Model:

For a long time, conventional medicine has been practiced with the belief that disease comes from abnormally functioning cells. The microscopic understanding of the cell and genetics led many to believe that when genes act abnormal, there is no way to go back. Drugs are designed to block abnormal activity of the cells. However, this model of treatment has backfired most of the time. Drugs are very forceful in their actions, often taking physiological controls away from the body’s natural wisdom. The uncontrolled drug activity results in side-effects for most individuals. Now, the new paradigm of genomics is beginning to realize that abnormal genetic expression is at the basis of the widespread abnormal cellular function.

Epigenetic studies, that look at the interaction between of cellular environment and genes, tell us a more than the eyes can see. We have learned that, while we are all born with genetic information from our parents, throughout our lives genetic expression is governed by the micro-environment that surrounds the cell. This surrounding micro-environment contains hundreds of chemical signaling molecules, like hormones, cytokines, etc., that travel from near and far to communicate with the cell. These signaling molecules travel all around the body to help synchronize the actions of all the organs. Majority of these signaling molecules that interact with the cells are derived from the foods we eat.

Nutritional genomics is the attempt of scientists to understand the interaction between our food and our genetic activity. Dr. Raymond Rodriguez, a leading researcher in genomic studies explains “Nutrigenomics seeks to provide a genetic understanding for how common dietary chemicals (i.e., nutrition) affect the balance between health and disease by altering the expression and/or structure of an individual’s genetic makeup.”

The some of the most effective dietary supplements, vitamin preparations, and other similar products are based on studies that look at how the particular food or nutrient affects the body. The powerful impact of the chemical compounds from natural foods and herbs have on the body is a result of the co-evolution of humans and plants. In other words, humans evolved a model of health that is complementary to food that was most easily available. Humans also evolved the physiology that could use nutrients from food for a medicinal effect. Therefore, human physiology is specifically designed to respond to the balancing and healing effects of the food we eat. Before the advent of modern drug industry, the kitchen was the most accessible pharmacy to people. Herbal supplements

used as an extension of dietary interventions. Rodriguez claims that using genetic studies to determine the susceptibility of individuals will allow us to prescribe functional foods as preventive medicine.

Cardiovascular disease has received a lot of attention in the nutritional genomic field. Researchers have been able to develop some individualized outlines for using specific fish oils, salt intake, mineral intake, carbohydrate and fat intake and much more.[4] These studies have been able to generate useful observations of how specific dietary components affect blood pressure, obesity, vascular plaques, and other components of heart disease.[4] Cancer is another disease that has demonstrated relationship to food-gene interactions.[5 ]Nutrients like vitamin D can help in proper activation and inactivation of genes. Methylated-folate can help with DNA methylation, which prevents abnormal expression of genes. Phytoestrogens from plant based foods can help to modulate effect of human estrogen; thus reducing risk of estrogen based cancers of breast, ovaries, cervix, etc. These discoveries are every exciting for the scientific-minded holistic practitioners. However, researchers admit that our knowledge and our ability to apply this knowledge is very limited at this time. Thus, in the west, nutritional genomics represents a hope for a future of scientific individualized medicine.

Ayurvedic insights to genomic individuality:

Vata, Pitta, Kapha
Figure 1

Individualized medicine is one of the core principles of Ayurveda. Scientists of India grappled with this requirement of medicine more than 5000 years ago. Ayurveda uses the Tridosha system to guide individualization of treatments. In the Ayurvedic system, each person is considered a unique combination of the five elements: Space, Air, Fire, Water, and Earth. The five elements combine to form, three physiological humors called Tridosha. These humors are Vata, Pitta, and Kapha (figure 1). Each humor possesses specific qualities that are reflected in their physiological functions. For example, Vata dosha – made up of Space and Air – is responsible for movement; Pitta dosha – made up of Fire – is responsible for digestion and other metabolic functions; Kapha dosha – made up of Earth and Water – is responsible for structure and stability.

Each individual has unique combination of these elements – which represent the unique combination of doshic qualities that the individual carries. These elements are expressed in the form of person’s body type, mental activity, emotional tendencies, and physiological functions. The Ayurvedic physicians, through the observation of these aspects of the individual, assess the unique combination of Tridosha, called the Prakriti or constitution.

The individuation described by the language of elements and Tridosha is a precursor of the modern genomic individuation. While lacking the modern technology, ancient Vedic scientists used the power of observation to discern the constitution of the individual. This observation requires powerful skills of being present with the patient, interviewing the patient, and examining the patient. Ayurvedic texts go into great details about symptoms, disease progression, physical examination; these details are then translated into the language of Tridosha. This informs the practitioner about genomic individuality (that is, Prakriti) of the person. In modern terms, the Prakriti or constitution of the individual is the sum expression of the individual’s genome. This individual genomic signature is expressed by the individual’s symptoms, likes and dislikes, mental and emotional tendencies, as well as physiological measures like lab/blood tests.

The legacy of this visionary work of Vedic scientists has streamed through Ayurveda for over 5000 years to the present scientific age. While faith and skill are adequate for the traditional Ayurvedic practitioners, modern minds demand scientific validation. In recent years, the study of “Ayurgenomics” has emerged to test validation of these claims. In one study, researchers performed genetic testing of individuals with 3 distinct constitutions: Vata, Pitta, or Kapha.[6] Scientists matched up the genetic study with the constitution to determine which genetic patterns emerged. The results demonstrated the following: Vata constitution individuals had more active transport components; Pitta constitution individuals had greater activity and responsiveness of blood components like various blood cells, platelets, immune cells, etc.; Kapha constitution had larger share of lipid components like cholesterol, triglycerides, as well as structural proteins. These results correlated with the qualities of doshas described in classical texts: Vata – movement, Pitta – metabolism, Kapha – structure and stability.

In another study, constitutional expression of people from different climates were tested.[7] Researchers focused on EGLN1 gene, which is an oxygen sensor that activates other genes that help the body adapt to low oxygen concentrations. Researchers anticipated that expression of EGLN1 gene would be greater in high altitude populations. Because this gene relates to adapting and oxygen metabolism, researchers also predicted this population may have higher numbers of Pitta individuals. The results validated both predictions: individuals in higher altitudes had greater expression EGLN1 gene and significantly higher numbers of Pitta individuals. This high altitude gene expression pattern and pitta constitution was also found to be prevalent in mountain people in other parts of the world.[8]

Yet another study applied the predictive value of Ayurgenomics to uncovering underlying cause of Rheumatoid Arthritis (RA).[9 ]In general, RA is expressed as inflammation and pain of joints. So, over-activation of inflammatory pathways is expected in all RA patients. However, Ayurveda predicts that underlying characteristics between Vata dominant and Pitta dominant individuals are likely very different. The results confirm constitutional based individuality. RA patients with Vata constitution and greater expression of inflammatory markers, IL-1β and TNF-ɑ; on the contrary, RA patients with Pitta constitution had greater expression of oxidative stress markers, SOD3 and PON1. Kapha constitution did not favor either inflammatory or oxidative pathways. Altogether, Ayurgenomics demonstrated capacity to clarify underlying mechanisms of destructive process of RA.

Conclusion:

The scientific advances of the modern generation have gone a long way to provide us deep and detailed insight of the microscopic world that is within us. The discovery of the sciences of Genomics and Epigenetics is beginning to demonstrate the relationships between the outer world, the inner world, and all the interactions between the two worlds. These sciences have brought us to the threshold of individualized holistic medicine. But, we are still figuring out their language and applications in health-care.

Vedic scientists recognized that we are all part and product of our environment. We are all in a relationship with the Earth, plants, animals, birds, bugs and the germs, as much as with people. The water we drink has been used by all manners of animals, birds, bugs, and germs. The air we breathe has been purified by plants. The foods we eat are derived from plant and animals alike. Our physiology, hormones cycles, and health are profoundly affected by the changing natural rhythms of the day-night, seasons, and even our age.

Ayurgenomics is based on an ancient and proven framework of the observational medicine that respects all these relationships and our place in nature. The language and foundation of Ayurgenomics is well established. It is being successfully used in Ayurvedic clinics across the world. This ancient language and wisdom are helping to fill the gaps that appear in the modern scientific disciplines. Studies have demonstrated the application of Ayurgenomics for predicting genomic variation among healthy individuals. It has also been validated to demonstrate individualized differences among people with the same disease.

We live in a very special time – Slowly but surely, we are reclaiming our ancient wisdom through the means of modern scientific inquiry.

References

  • [1] The Tech Museum of Innovation. “Genes in Common”, the Department of Genetics, Stanford School of Medicine online article.
  • [2] Kaput J and Rodriguez R. Nutritional genomics: the next frontier in the postgenomic era. Physiol. Genomics, 2004; Vol. 16, Pg. 166-177. doi:10.1152/physiolgenomics.00107.2003.
  • [3] Mayo Clinic Staff. “Diseases and Conditions: Phenylketonuria” online article.
  • [4] Corella D and Ordovas JM. “Nutrigenomics in Cardiovascular Medicine.” Circ Cardiovasc Genet. 2009; Vol. 2, Pg. 637-651.
  • [5] Ross SA. “Nutritional genomic approaches to cancer prevention research.” Exp Oncol. 2007 Dec; Vol. 29(4), Pg. 250-6.
  • [6] Prasher B, et al. Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda. Journal of Translational Medicine 2008; Vol. 6(48), Pg. 1-12.
  • [7] S Aggarwal, et al. EGLN1 involvement in high altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda Proc. Natl. Acad. Sci. U S A. 2010 Oct 18. (2010).
  • [8] Mukherji M and Prasher B. Ayurgenomics: A New Approach in Personalized and Preventive Medicine. Science and Culture Journal, 2011; Vol. 77(1-2), Pg. 10-17
  • [9] Juyal RC, et al. Potential of Ayurgenomics Approach in Complex Trait Research: Leads from a Pilot Study on Rheumatoid Arthritis. Plos ONE, 2012; Vol. 7(9), e45752.