No two individuals respond the same way to diet and exercise. One person may eat pasta every day, hardly exercise, and never gain a pound. While another might train for a marathon and eat a balanced diet but struggle to lose weight. Yet, nutritional guidelines and standards tend to treat everyone the same.

As more people are realizing that one size does not fit all, personalized health is taking off. Scientists are starting to understand the molecular changes that underlie the differences in each person’s response to medications or lifestyle changes, and new technology is making monitoring and testing of individuals possible.

Some of the most visible players in the area use genetic testing. Genome sequencing is becoming faster and more affordable, and as a result, the knowledge of the human genome is expanding rapidly, allowing genetic testing companies like 23andMe and Ancestry to become household names. Now, anyone can learn about their ancestry and survey a panel of genetic health markers with a fairly affordable home test.

Although 23andMe tests for several markers associated with weight gain, most of the markers in its panel predict for disease risk. One example is macular degeneration, a cause of vision loss that could affect an individual at some point in the future, but does not affect health on a daily basis. Beyond determining risks for diseases that may affect them in their old age, many people are concerned about how they can lose weight now.

According to CDC estimates, 139 million American adults (42%) are obese and 34 million Americans have diabetes. Every year, Americans spend upwards of $60 billion on gym memberships, diet plans, and other services dedicated to weight loss. But for many, sticking to a diet is a problem, and for some, knowing where to start can be challenging. Could a personalized diet plan based on genetic testing and real-time monitoring be a helpful tool?

The practice of collecting health data on a daily basis is not new, as evidenced by the trending use of fitness trackers, body composition testing, and diet apps. There are more than 20 companies in the global fitness app market, which is expected to reach $14.6 billion by 2027. Health apps are built and run on population level data that don’t necessarily apply to all individuals. For example, Fitbit uses simple metrics such as height, weight, age, and sex to calculate how many calories are burned in a workout or need to be consumed on a daily basis. As such, these guidelines are sufficient to help only a subset of individuals optimize their diet and exercise. But to reach a certain weight loss goal or improvement in athletic performance in all individuals, more accurate metabolic measurements and tailored guidelines are needed.

Nutrigenomic Testing

Nutrigenomic testing is based on the same principles used by ancestry testing services. After a customer submits a saliva sample, their DNA is extracted and analyzed using a panel of known single nucleotide polymorphisms, or SNPs. SNPs are single variations at specific locations in the human genome, some of which are associated with specific traits or diseases.

In nutrigenomics testing, DNA is analyzed with an array of SNPs associated with nutritional needs and metabolism. For example, certain SNPs in the VDR and GC genes indicate that an individual has lower than average levels of calcium absorption because the proteins encoded by these genes help respond to and transport vitamin D, which is needed for calcium uptake.

After analyzing SNPs, the company generates a report that summarizes the customer’s genetic results and provides a tailored diet plan. The report includes information on optimal intake of macronutrients (carbs, protein, fats), specific requirements for various vitamins and minerals, and specific intolerances to food components such as lactose or caffeine. So for individuals with SNPs in VDR and GC that indicate lower than average levels of calcium absorption, a nutrigenetics report would recommend consuming more calcium than the recommended daily value and provide a catalog of calcium-containing foods.

There are currently more than 70 companies involved in nutrigenomics testing. One of those, Milwaukee-based GenoPalate, offers at-home testing and provides the consumer with personalized nutrition recommendations. For $150, the consumer will have their at-home test analyzed for more than 100 genetic alleles and receive a streamlined report detailing the importance of different nutrients, the individual’s genotype, and its implications for specific dietary recommendations. For $180, the consumer can also receive five recipes tailored to them.

GenoPalate CEO, Yi Sherry Zhang, PhD, is keen on tackling the problem of obesity in America. “Our focus is to prevent chronic illness,” Zhang says. As she sees it, nutrition research needs to move in a more personal direction. “Medicine is being practiced as the average of other people versus you and you are the 100% that the outcome really matters to.”

Zhang’s team of scientists works to develop GenoPalate’s panel of genetic variants by combining research evidence from published studies and optimizing over time. They are also working to incorporate data formats other than their own. For example, any of the more than 10 million people who have done testing with 23andMe can import their data and have it reanalyzed for nutritional information at a reduced cost ($40-70). GenoPalate has analyzed more than 50,000 nutrition profiles and is growing quickly. They have added 7- to 8-fold more customers compared to 2019—another indicator that the world of personalized medicine is on the rise.

Nutrigenomix, based in Toronto, is another nutrigenomics company that has been at the forefront of the field. Since its founding in 2011, Nutrigenomix has expanded its original panel of 7 genetic markers to 70, all of which have been validated by rigorous peer-reviewed studies. Like GenoPalate, each report—which you can get for about $400—not only contains genotypes and recommendations, but also provides a fully customized meal plan and consultation with a registered dietician. Nutrigenomix only offers their testing through health practitioners in order to help consumers interpret the complex panel of genetic information they receive and implement a diet plan in their daily lives.

Nutrigenomix differentiates itself from other competitor products by providing its nutritional guidelines based on the consumer’s goals. “The personalized recommendations are always customized to the individual’s genetic test results, but their focus may differ depending on their ultimate health and wellness goals,” says founder and CSO Ahmed El-Sohemy, PhD. Customers can opt to receive recommendations on health and weight management, athletic performance, fertility, and plant-based diets.

However, the main goal for nutrigenomics companies is not to treat significant health problems. Both GenoPalate and Nutrigenomix attract customers who already have an interest in health and wellness and are looking to improve their nutritional guidance in small ways. As with other personal fitness and nutrition apps, the focus is on prevention and holistic health—a philosophy that is slowly gaining traction in the US.

A multi-faceted approach

Though nutrigenomics testing has the potential to reveal insights into how the body processes foods and to alter eating habits, it is far from a silver bullet. Individual genetic sequencing is still a relatively new concept and there is a lot to learn in the field.

“The challenge with all of this stuff is it’s really, really difficult to study,” says Elena Flowers, Associate Professor of Physiological Nursing at UCSF. For example, Flowers explains, a number of genetic risk factors for type II diabetes are worse predictors than family history. Genetic information might shed light on how diabetes develops and help refine diagnostic categories, but it won’t necessarily help with the actual diagnosis.

Likewise, a single genotype gives insight into only a small part of how the body actually responds to a food or metabolizes a nutrient—both of which are complex processes involving many genes and other metabolic factors. Combining genetic information with other measurements may be a more useful way to evaluate these processes.

Epigenetics

To understand why building a diet plan around SNPs is imperfect requires an understanding of epigenetics; changes in gene expression caused by non-genetic factors. Even if a SNP is found in a metabolic gene, it may not affect how that gene is expressed because of epigenetics.

Environmental factors like exercise can play into epigenetic changes. For example, exercise increases DNA methylation—which usually indicates decreased gene expression—at thousands of sites in the genome, including some that indicate risk for obesity and type II diabetes. Exposure to toxins or oxidative stress over the span of a lifetime can also impact the body. There is currently no accurate way to measure the impact of such exposures, collectively called the “exposome,” on the body.

However, El-Sohemy argues that there are some genes whose expression patterns are affected by environmental factors but still affect nutrient response the same way. Take the CYP1A2 gene, for example, in which a certain SNP can predict if someone metabolizes caffeine slowly. Various external factors such as smoking and hormonal contraception have been shown to increase or decrease CYP1A2 gene expression, respectively, but “we still see an independent effect of CYP1A2 genotype on modifying the effects of caffeine,” says El-Sohemy.

Gut microbiome sequencing

 The microbes that live in the human gut perform a variety of functions, such as breaking down complex sugars or producing vitamins needed for cell function, which can have a large impact on how certain foods are metabolized. While the composition of the gut microbiome can change over time, it is actually fairly resilient. There are several companies working on gut microbiome sequencing, like Sun Genomics and myBioma.

Gut microbiome reports contain a list of microbes in an individual’s gut and their corresponding proportions, as well as nutritional recommendations based on what those microbes are known to do, like their ability to metabolize sugar. Pairing gut microbiome analysis with genomic analysis could add value to metabolic information. For example, fiber intake can help prevent diabetes by a 2-pronged approach: promoting growth of certain microbes, and influencing the expression of genes that predict diabetes risk. Deciding on a recommended fiber intake may require taking both microbes and host genes into account.

 Metabolomics

After eating and exercising, thousands of metabolites are produced in the human body by both our own cells and gut microbiota. Their effect on health is currently unclear. However, Michael Snyder, Chair of the Stanford University Genetics Department, expresses that glucose spiking and food logs are more beneficial for the average person than nutrigenomics testing. “Knowing what foods spike your glucose, spike your lipids, that seems to be more direct information that you could act upon,” Snyder states.

The challenge with understanding metabolites is that the entire metabolome cannot be measured with one test. Specific assays must be designed for each metabolite, and since metabolite levels fluctuate dynamically, testing would need to be done multiple times, likely with the supervision of a physician. These factors make it much more difficult to integrate metabolomics into the health and fitness app market.

A holistic approach

Currently, nutrigenomics might be useful to those seeking to make small improvements in performance, like athletes, or those who are already highly invested in their diet. Even if a customer doesn’t see changes on a daily basis, it is likely that their body is still responding to the guidance and will be healthier in the long run.

However, every day new studies recommend small lifestyle changes that presumably improve long-term health, making it seemingly impossible to maintain all of the recommended habits consistently. Ultimately, basic changes to eating habits and exercise remain an easier route to improved health. “As long as people adhere to a diet they do better,” says Flowers.

While nutrigenomics companies offer a promising service, there is still more to be learned about how genes play into metabolic processes. “Your immunome, metabolome, and microbiome are all so inter-related,” says Snyder, explaining that differences between those “omes” are probably driven by epigenetic changes influenced by food and lifestyle. Nutrigenomics will be most useful as one part of a whole that accounts for all of these factors. There is a strong push for truly personalized nutrition and plenty of room for new developments to help humans achieve their best.

Hayley McCausland, BS is a PhD candidate in Molecular and Cell Biology at the University of California, Berkeley.