Nutrigenetics, Weight Management, and Dietary Supplements

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Could knowledge of our individual genetic variants guide us in making better, more personalized lifestyle choices, including the foods we eat and the dietary supplements we take? And could we leverage this information to mitigate our individual risk of obesity and other conditions? Experts in the fields of genetics, microbiology, the “-omics” (including metabolomics, proteomics, and more) and nutritional science generally say yes-but their opinions differ on what conclusions we can draw now with the information we currently have in this field, and how and when the science will be translatable into meaningful, scientifically sound commercial applications.

Much more than a trendy buzzword, nutrigenetics “has as its main goal to understand the gene-based differences in response to dietary components and to develop recommendations that are the most compatible with the health status of individuals based on their genetic makeup,” explains José M. Ordovás, PhD, director, Nutrition and Genomics, and professor, Nutrition and Genetics, at the Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University (Boston). Another way of putting it? “Nutrigenetics is about how individual responses to food are driven by genetic differences.”

Hooman Allayee, PhD, professor, Departments of Preventive Medicine & Biochemistry and Molecular Medicine, at the Keck School of Medicine, University of Southern California (Los Angeles), and president-elect, International Society of Nutrigenetics/Nutrigenomics, adds, “Nutrigenetics asks, ‘Do the DNA differences between any two people make them respond differently to nutrients?’ The concept is based on relating genetic differences at the DNA level to the response to nutritional components.”

This science is poised to disrupt the nutrition field and its blanket public-health guidelines as we now know them, and the potential applications hold tantalizing appeal for industry and consumers alike. “The ultimate personalized nutrition comes, of course, from nutrigenetics,” Ordovás says.

Characterizing the field as “extremely complex,” Ordovás explains that while he and his colleagues have been studying nutrigenetics for decades, it is, in his opinion, “still in its infancy” from a practical perspective. Early on, progress was limited by more-primitive technology and poor knowledge of the human genome, Ordovás says. Since then, technology has “vastly improved,” and our knowledge of the human genome is better-“though rather incomplete.”

“Still,” Ordovás says, “we have to integrate nutrition and genetics using very solid scientific approaches if we want the field of nutrigenetics to mature and yield meaningful solutions and applications.”
 

Nutrigenetics & Weight Management: What We Know, What We Have Still to Learn

The question, “What do we currently know about nutrigenetics, particularly related to obesity and weight management, and what can we do with that knowledge?” yields varying answers depending on whom you ask. A portion of an American Heart Association statement published in the journal Circulation: Cardiovascular Genetics in 2016 and to which both Ordovás and Allayee contributed reads, “Nutrigenomics has the potential to identify genetic predictors of disease-relevant responses to diet, and this potential and its applicability in the context of personalized nutrition have popular appeal. However, nutrigenomics has also been the subject of much hyperbole and has been ascribed much promise, particularly in the arenas of personalized nutrition, functional foods, and nutraceuticals. Unfortunately, the science has not yet fully delivered on this unrealized potential.” The statement does acknowledge “enthusiasm about possible clinical applications” but maintains that “the evidence base remains limited.”

While the tone of that particular statement is one of cautious optimism, Tufts’ Ordovás does, in comments shared with Nutritional Outlook, point to “promising findings related to nutrigenetics and weight management,” including research performed at Tufts University that concluded that limiting saturated-fat intake may help promote healthy body-mass index (BMI) especially in people whose genetic makeup increases their risk of obesity.¹ (For this study, researchers identified 63 gene variants related to obesity and used them to calculate a genetic-risk score for obesity for more than 2800 white adults. Participants with a higher genetic-risk score who also consumed more of their calories as saturated fat were more likely to have a higher BMI, the researchers found.)

“Genetic-risk score could be useful in identifying people who are predisposed to obesity and could ultimately lead to personalized dietary recommendations,” reads a Tufts press release about the study, which was published in 2014 in the Journal of the Academy of Nutrition and Dietetics.
 

All Eyes on FTO

Several genes associated with risk of obesity have been found in large studies, including FTO, MC4R, TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, and NEGR1, USC’s Allayee says. The FTO gene in particular is the subject of some studies cited by Ahmed El-Sohemy, PhD, professor and Canada research chair in nutrigenomics, Department of Nutritional Sciences, at the University of Toronto, in comments e-mailed to Nutritional Outlook.

In one of these, “FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: the POUNDS LOST Trial,” a randomized, controlled study published in the journal Diabetes in 2012, the authors wrote, “We found that dietary protein intake might modify the FTO variant’s effect on changes in body composition and fat distribution.”² Specifically, “a high-protein diet may be beneficial for weight loss in individuals with the risk allele of an FTO variant.”

El-Sohemy, who founded a company called Nutrigenomix, which provides customers with genetic testing and subsequent lifestyle advice based on test results, says that FTO in particular has also been shown to determine whether a person is more or less likely to lose weight by altering the amount of saturated and unsaturated fat in his or her diet.³ “And another factor that has been linked to the FTO gene is metabolic response to physical activity,” he adds.

El-Sohemy acknowledges that “the FTO gene alone is not a very strong predictor of whether or not a person will become obese,” an opinion with which USC’s Allayee agrees. “There are just too many factors-social, environmental, genetic, et cetera-that affect a person’s risk. But knowing which version of the FTO gene a person has can help determine whether they are likely to benefit from certain dietary changes, or whether they need to focus on another aspect of their diet,” El-Sohemy contends.

Knowing one’s FTO status could also be useful simply as a behavioral motivator for those seeking to lose weight, according to a finding published in the American Journal of Clinical Nutrition this year.⁴ Results from the randomized, controlled Food4Me European trial showed that when an individual is provided information about his or her FTO-gene status (specifically, whether he or she carries the obesity-risk allele) in addition to dietary advice, that individual loses more weight than someone provided dietary advice alone.

“That study,” explains Allayee, “showed that if you inform people that they are genetically susceptible, and if you give them the genetic info, it makes people more aware, and they are more likely to stick to dietary recommendations,” whatever those recommendations may be.
 

Beyond FTO: New Research Begins on a Liver-Fat Gene

Turning their attention to a potential nutrigenetic association within a segment of the pediatric population, Allayee and colleagues are currently recruiting participants for a study that examines whether reducing sugar consumption in children at genetic risk for developing fatty liver decreases their amount of fat in the liver at the end of six months.⁵

“Fatty liver is a big problem in Hispanic children who tend to be overweight or obese,” Allayee explains. “We found that if you carry the genetic variant that increases liver fat [GG genotype of gene PNPLA3], it was especially bad for kids who had a lot of sugar in their diets. That’s another nutrigenetic association.”

If the researchers’ hypothesis (that reducing sugar will reduce liver fat in children who carry the risk allele) is correct, there could be valuable clinical applications in terms of personalizing dietary recommendations for these children and their families. “That’s where the field has to go,” Allayee says.
 

Industry Participation

While leveraging existing nutrigenetic findings for the creation of commercial personalized-nutrition and -lifestyle products and recommendations is not condoned by some in academia, others disagree and are doing just that.

El-Sohemy’s University of Toronto−based biotech startup, Nutrigenomix, offers a genetic test (made available through participating healthcare providers) that analyzes an individual’s DNA through a saliva sample and tailors personalized dietary and lifestyle recommendations based on the results. The Nutrigenomix test includes 45 genetic biomarkers, including those related to FTO variants and weight management.

El-Sohemy stands behind his company’s product and maintains that there is currently “plenty of evidence to show that we can give specific recommendations for those with the FTO risk variant.” He cites the previously referenced POUNDS LOST Trial as well as another study published in the Journal of Nutrigenetics and Nutrigenomics in 2015 that connects a low-carbohydrate, high-protein diet with better weight-management results in individuals with the FTO risk allele.⁶ A Diabetes piece published the same year analyzed 16,000 children and adolescents from 14 studies and reached the same conclusion, El-Sohemy adds.⁷

Another industry player who is already applying nutrigenetic findings to a commercial personalized-nutrition program is Amway, the direct-selling business based in Ada, MI, that was worth $8.8 billion in 2016. Amway offers a genetic test and subsequent lifestyle recommendations and related food and supplement products as part of its BodyKey by Nutrilite line. BodyKey was launched in the United States in 2013.

Nick Wasmiller, PR lead, Global Media Relations at Amway, explains that the genetic test that is part of the BodyKey Jump Start kit in the United States and Europe is provided by Inherent Health (an Interleukin Genetics brand) and includes gene testing related to weight management. Based on an individual’s test results, BodyKey recommends a particular dietary plan (such as reduced carbohydrates or reduced fat) plus BodyKey food products (such as snack bars) and Nutrilite supplements (such as Nutrilite CLA 500). Forty-nine percent of Amway’s 2016 sales were in the nutrition category, up 3% from 2015, and its Nutrilite line of supplements is one of its top-selling brands.

On the supplier side, BASF Corp. is paying close attention to the field of personalized nutrition and the science behind it, including nutrigenetics. The company offers its Newtrition line of ingredients for supplement brands. The Newtrition line includes, among other ingredients, Tonalin CLA, which the company states on its website is “clinically shown to help reduce body fat up to 10%, while increasing lean muscle mass and preventing fat regain.”

John Helfrick, director, Human Nutrition, BASF Nutrition & Health, North America (Florham Park, NJ), says that BASF “realizes the importance personalized nutrition will have on demand and will continue to innovate with [companies ranging from] startups to major brand owners to support the science and develop novel ingredients to meet evolving needs.” He continues, “Personalized nutrition offers tremendous opportunities for marketers and manufacturers, and BASF will continue to work with them to differentiate their health-enhancing products.”
 

Moving Forward

Opinion is mixed on how much nutrigenetic evidence is required to personalize an individual’s diet and supplementation for weight management, cardiovascular health, and other concerns. “I certainly think there are personal-nutrition recommendations one can give for obesity or heart disease or cholesterol, et cetera,” says Allayee. “But we haven’t figured out which ones those are yet.” Certain recommendations “are not yet ready for prime time,” he adds.

Ordovás says of nutrigenetics in general and weight management in particular, “FTO is one of many genes involved. We need to pool the information from different genes in order to achieve practical solutions.”

And Allayee concludes, “I would say to supplement makers and functional-food brands that clearly there could be very important clinical applications for this field. We’re not at that point yet, but if you are interested in it, then please get involved. Support the academic teams studying nutrigenetics and nutrigenomics; invest in advancing the science.”

El-Sohemy offers a different, perhaps less-conservative perspective: “There’s always the need to say that we need to learn more, and we need to do more research. I agree. But, there comes a time where we need to ask, ‘How much more evidence do we need?’ We currently give advice on what to eat, which is based on ‘old’ science from ten to twenty years ago. If we now have science that enables us to provide better advice for individuals-not just one-size-fits-all for the entire population-then shouldn’t we do that?”
 

Sidebar: Industry Welcome at Annual ISNN Congress
The 11^th Annual Congress of the International Society for Nutrigenetics/Nutrigenomics will take place September 16-19, 2017, in Los Angeles. “It’s meant for scientists, clinicians, and registered dieticians, but we also want industry participation,” ISNN President-Elect Hooman Allayee, PhD, explains, “because industry has to look at where the science is and be aware of it.”
More information is available at ISNN’s 11th Annual Conference website, www.nutritionandgenetics.org/ISNN2017.

References:

1. Casas-Agustench P et al., “Saturated fat intake modulates the association between an obesity genetic risk score and body mass index in two US populations,” Journal of the Academy of Nutrition and Dietetics, vol. 114, no. 12 (December 2014): 1954-1966
2. Zhang X et al., “FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: the POUNDS LOST Trial,” Diabetes, vol. 61, no. 11 (November 2012): 3005-3011
3. Phillips CM et al., “High dietary saturated fat intake accentuates obesity risk associated with the fat mass and obesity-associated gene in adults,” Journal of Nutrition, vol. 142, no. 5 (May 2012): 824-831
4. Celis-Morales C et al., “Can genetic-based advice help you lose weight? Findings from the Food4Me European randomized controlled trial,” American Journal of Clinical Nutrition. Published online April 5, 2017.
5. Goran MI and Allayee H, “Nutrigenetic Intervention to Reduce Liver Fat in Hispanics.” Research project currently underway at University of Southern California, Los Angeles. Funded by NIH, National Institute on Minority Health and Health Disparities.
6. De Luis DA et al., “Effects of a high-protein/low-carbohydrate diet versus a standard hypocaloric diet on weight and cardiovascular risk factors: role of a genetic variation in the rs9939609 FTO gene variant,” Journal of Nutrigenetics and Nutrigenomics, vol. 8, no. 3 (November 2015): 128-136
7. Qi Q et al., “Dietary intake, FTO genetic variants, and adiposity: a combined analysis of over 16,000 children and adolescents,” Diabetes, vol. 64, no. 7 (July 2015): 2467-2476