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Nutrigenetics and Weight Loss

Recently, a small trial (1) testing the efficacy of nutrigenetics-based dietary advice for weight loss was published and made its way around twitter. I saw a number of people saying "weight loss is weight loss, you don't need special diets" or things of the sort, kind of downplaying the potential of nutrigenetics. I'm pretty realistic about nutrigenetic-based dietary counseling, if you've read my December post for Alan Aragon's Research Review. But I wanted to comment on this study since I found it pretty disappointing, and people's reactions toward it were pretty 'poo poo' -ey about nutrigenetics.

In general, the consensus is that the science isn't there to support nutrigenetics-based dietary counseling (2). I'd argue that, for complex traits (eg prevention of chronic disease, weight loss) the science really really isn't there. Even for more deterministic polymorphisms in simpler pathways (eg. CYP1A2 variants affecting caffeine metabolism), we still need better clinical trials looking at relevant outcomes. Given this info, I was kind of surprised to see a nutrigenetics based dietary counseling study, and at the same time, wasn't surprised that it failed. I wasn't aware of any studies showing that scientists had discovered significant gene-x-nutrient interactions that would require one type of diet over another for weight loss.

Looking at this study, there's a couple reasons that I'm not surprised that it failed to show anything significant:

1. Power - This was more a feasibility trial. Only 32 of the original 50 recruit study participants completed this two-armed trial, leaving it relatively underpower to see differences. The authors note in their discussion that for them to have detected the observed 3.2% difference in individuals achieving >5 percent weight loss between groups in the study, they would've needed 336 participants in each group to have 80% power at an alpha of .05.  Read: even if there would be an effect to this design, we couldn't statistically see it. The study was also underpowered to detect an effect of adherenece on weight loss. (note: I don't blame the authors for this - there's not a lot of previous data on nutrigenetics based weight loss to have based power calculations off of). The authors don't report the power needed to detect differences in non-weight loss outcomes, but I imagine we'd run into power issues..and adherence ones (see below).

2. Genotypes - As I noted above, I wasn't aware of any data suggesting that a nutrigenetics-based weight loss diet would be effective. As soon as I saw the study, I went right to their section on which genotypes were used to design these diets.

None of these variants change the basics of energy balance, and none provide any insight into how different macronutrient compositions might interact uniquely with individual genotype and affect nutrient partitioning/body composition. At best, they may affect lipoprotein responses or glucose/insulin dynamics. Even for those references that are related to body weight, it's weak data: their APOA2 polymorphism reference (3) comes from cross-sectional data looking at interactions between this polymorphism and dairy fat, linking it to a higher BMI - hardly causal.  I'm not totally sure why someone would expect that giving this kind of genetic-based dietary intervention would enhance weight loss..unless it affected adherence. 

*This was fixed in the final version* One should note that this is quite sloppy referencing: Reference 16 is listed next to Apo A-II, yet it links to a circulation study on hepatic lipase. Reference 20 is for ppar-gamma, yet its listed as evidence for FTO. Reference 22 is about ApoA2 but cited for FTO. 26 is about the FTO genotype, but its cited as evidence for ppar. I could go on but you get the point. Sloppy.

3. Adherence and Diets - The trial didn't really do much to ensure individuals were adherent to diets. The trial used HealthyChoice entrees for lunch/dinner and collected receipts to measure adherence, which looked overall higher in the control, standard therapy group... If people aren't adherent (and we can't tell very well how adherent they are) to a nutrigenetics diet, should we expect them to have better outcomes? Furthermore, you might expect that if you're designing a trial that gives 4 different diets based on macronutrient composition to vary a bit in those compositions...but.... well i'll let you decide what we should've expected based on these:


The promise of nutrigenetics is in its ability to understand individual physiological responses to diets differing in their macronutrient/micronutrient compositions, not in its ability to defy thermodynamic - let's judge genetic-based dietary counseling on well powered trials with smart genotypes and sensible outcomes.

I'm all for nutrigenomics research and foresee a lot of promise - let's make sure we're not pushing the technology though (4).

1. http://www.sciencedirect.com/science/article/pii/S1542356515002505
2. http://www.ncbi.nlm.nih.gov/pubmed/23471854
3. http://www.ncbi.nlm.nih.gov/pubmed/24108135
4. http://www.ncbi.nlm.nih.gov/pubmed/25342299

Comments

  1. SebMarch 23, 2015 at 4:14 AM

    Good post.
    I am collaborating on a similar but larger study and although I cannot say anything specific about it I can tell you that your concern about insufficient power is not what explains the lack of positive results here...

    Your concerns #2 and #3 are most likely the reasons we see no real effect of "nutrigenetics"-based weight loss diets.

    ReplyDelete
  2. Nutrition TrackerJune 2, 2015 at 6:10 AM

    Weight loss can be achieved by balancing a healthy level of physical activity with eating a nutritious diet.

    ReplyDelete
  3. AnonymousSeptember 9, 2015 at 7:53 PM

    Sloppy referencing has been fixed in the final published version.

    ReplyDelete
  4. androdiolDecember 21, 2015 at 11:02 AM

    Now that is something I call a progress. I also want to get same body and it will be great to have some tips from you for that. It will be better if you can share some androdiol supplement

    ReplyDelete

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