Evidence from Inuits Suggests 'Best' Diet May Depend on Your Genes

[Dean Pomerleau]

All,

 

One of the initial motivations for studying the possible benefits of the Omega-3s PUFAs DHA & EPA came from observations that the Inuits of Greenland, whose diet contains a very high proportion of polyunsaturated fat from cold-water fish and marine mammals, suffer from relatively low rates of cardiovascular disease. But randomized control trials of the benefits of DHA / EPA supplements for (primary or secondary) prevention of cardiovascular disease have generally been disappointing (e.g. [1]).

 

This new study [2] in Science, might suggest at least part of the explanation for this apparent paradox. That paper used population-genetic analysis of Greenland Inuits to discover regions of two chromosomes that seem to have experienced strong selection in the recent past. Those regions also happen to contain genes involved in fatty acid metabolism; and the variants of the genes that have increased in frequency in Inuits are also associated with small stature and lower weight. From the abstract:

 

 By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of

growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.

 

In an accompanying commentary, there is a fascinating map of relatively recent human genetic variations and where they occur around the world (click to enlarge):

 

 

The one that isn't shown that I find very interesting is the salivary amylase gene (AMY1) for digesting starch. Several studies (e.g. [3]) have found that the number of duplicates of the AMY1 a person has can vary from 2 to about 15 from one individual to the next. The more AMY1 copies you have, the better you are at digesting starch / carbohydrates, and the less prone you are to obesity [3]. Study [4] looked at how the number of AMY1 copies varied between people of different ethnic groups and found a striking correlation between the amount of starch in their ancestral diet and the number of AMY1 copies their genome contained. Here is that result illustrated on a map (click to enlarge):

 

 

In short, it appears that in cultures whose ancestral diet contained a large fraction of carbohydrates, more copies of the AMY1 gene were selected for since it helped them better process carbs.

 

The bottom line appears to be that there is no "one size fits all" diet that is right for everyone. To some extent at least, the best diet for an individual depends on his/her genes.

 

--Dean

 

--------------------------------

[1] Arch Intern Med. 2012 May 14;172(9):686-94. doi: 10.1001/archinternmed.2012.262.

Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and
docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a
meta-analysis of randomized, double-blind, placebo-controlled trials.

Kwak SM(1), Myung SK, Lee YJ, Seo HG; Korean Meta-analysis Study Group.

Collaborators: Myung SK, Ju W, Oh SW, Bae JH, Kim YK, Park CH, Jeon YJ, Lee EH,
Chang YJ, Park SM, Eom CS, Lee YJ, Jung HS, Kwak SM.


BACKGROUND: Although previous randomized, double-blind, placebo-controlled trials
reported the efficacy of omega-3 fatty acid supplements in the secondary
prevention of cardiovascular disease (CVD), the evidence remains inconclusive.
Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and
docosahexaenoic acid in the secondary prevention of CVD.
METHODS: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two
of us independently reviewed and selected eligible randomized controlled trials.
RESULTS: Of 1007 articles retrieved, 14 randomized, double-blind,
placebo-controlled trials (involving 20 485 patients with a history of CVD) were
included in the final analyses. Supplementation with omega-3 fatty acids did not
reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI,
0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction,
congestive heart failure, or transient ischemic attack and stroke. There was a
small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99),
which disappeared when we excluded a study with major methodological problems.
Furthermore, no significant preventive effect was observed in subgroup analyses
by the following: country location, inland or coastal geographic area, history of
CVD, concomitant medication use, type of placebo material in the trial,
methodological quality of the trial, duration of treatment, dosage of
eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation
only as treatment.
CONCLUSION: Our meta-analysis showed insufficient evidence of a secondary
preventive effect of omega-3 fatty acid supplements against overall
cardiovascular events among patients with a history of cardiovascular disease.

PMID: 22493407

 

-----------------

[2] Science. 2015 Sep 18;349(6254):1343-1347.

Greenlandic Inuit show genetic signatures of diet and climate adaptation.

Fumagalli M(1), Moltke I(2), Grarup N(3), Racimo F(4), Bjerregaard P(5),
Jørgensen ME(6), Korneliussen TS(7), Gerbault P(8), Skotte L(2), Linneberg A(9),
Christensen C(10), Brandslund I(11), Jørgensen T(12), Huerta-Sánchez E(13),
Schmidt EB(14), Pedersen O(3), Hansen T(15), Albrechtsen A(16), Nielsen R(17).

The indigenous people of Greenland, the Inuit, have lived for a long time in the
extreme conditions of the Arctic, including low annual temperatures, and with a
specialized diet rich in protein and fatty acids, particularly omega-3
polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of
adaptation revealed signals at several loci, with the strongest signal located in
a cluster of fatty acid desaturases that determine PUFA levels. The selected
alleles are associated with multiple metabolic and anthropometric phenotypes and
have large effect sizes for weight and height, with the effect on height
replicated in Europeans. By analyzing membrane lipids, we found that the selected
alleles modulate fatty acid composition, which may affect the regulation of
growth hormones. Thus, the Inuit have genetic and physiological adaptations to a
diet rich in PUFAs.

Copyright © 2015, American Association for the Advancement of Science.

PMID: 26383953

 

-----------------

[3] Nat Genet. 2014 May;46(5):492-7. doi: 10.1038/ng.2939. Epub 2014 Mar 30.

Low copy number of the salivary amylase gene predisposes to obesity.

Falchi M(1), El-Sayed Moustafa JS(2), Takousis P(3), Pesce F(4), Bonnefond A(5),
Andersson-Assarsson JC(6), Sudmant PH(7), Dorajoo R(8), Al-Shafai MN(9), Bottolo
L(10), Ozdemir E(3), So HC(11), Davies RW(12), Patrice A(13), Dent R(14), Mangino
M(15), Hysi PG(15), Dechaume A(16), Huyvaert M(16), Skinner J(17), Pigeyre M(18),
Caiazzo R(18), Raverdy V(13), Vaillant E(16), Field S(19), Balkau B(20), Marre
M(21), Visvikis-Siest S(22), Weill J(23), Poulain-Godefroy O(16), Jacobson P(24),
Sjostrom L(24), Hammond CJ(15), Deloukas P(25), Sham PC(11), McPherson R(26), Lee
J(27), Tai ES(28), Sladek R(29), Carlsson LM(24), Walley A(30), Eichler EE(31),
Pattou F(18), Spector TD(32), Froguel P(33).

Comment in
Nat Rev Endocrinol. 2014 Jun;10(6):312.

Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic
associations compared to their biallelic counterparts. Here we investigated the
influence of gene dosage effects on adiposity through a CNV association study of
gene expression levels in adipose tissue. We identified significant association
of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body
mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects.
Increased AMY1 copy number was positively associated with both amylase gene
expression (P = 2.31 × 10(-14)) and serum enzyme levels (P < 2.20 × 10(-16)),
whereas reduced AMY1 copy number was associated with increased BMI (change in BMI
per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 × 10(-10)) and obesity risk
(odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) =
1.13-1.26; P = 1.46 × 10(-10)). The OR value of 1.19 per copy of AMY1 translates
into about an eightfold difference in risk of obesity between subjects in the top
(copy number > 9) and bottom (copy number < 4) 10% of the copy number
distribution. Our study provides a first genetic link between carbohydrate
metabolism and BMI and demonstrates the power of integrated genomic approaches
beyond genome-wide association studies.

PMID: 24686848

 

-------------------------

[4] Perry, G. H., Dominy, N. J., Claw, K. G., Lee, A. S., Fiegler, H., Redon, R., et al. (2007). Diet and the evolution of human amylase gene copy number variation. [10.1038/ng2123]. Nat Genet, 39(10), 1256-1260.

Edited September 19, 2015 by Dean Pomerleau

[Dean Pomerleau]

Here is a little more information on the Inuit study, from this article:

 

The study's findings suggest the Arctic people's genes evolved a certain way. It allows them to eat more fat than most other ethnic groups.

 

Researchers discovered a critical group of genes. They control how much omega-3 and omega-6 a person's body produces naturally.

 

Biologist Rasmus Nielsen was the lead researcher. He explained that almost all of the Inuit in the study had gene variations that could slow down the body's production of omega fatty acids, according to NPR.   

 

The genes also seem to help lower "bad" low-density lipoprotein (LDL) cholesterol, which is linked to heart disease. It also resulted in lower blood sugar levels, which decreases the risk of diabetes.  

 

In addition, the gene mutations lowered the Inuit's height by almost an inch (2 centimeters). This could be due to fatty acids affecting growth hormones, according to Phys.org.

 

Just 15 percent of Chinese and 3 percent of Europeans had those gene biomarkers.

 

So it looks like rather than or in addition to handling dietary fat in the bloodstream better, the Inuits have a gene variant than reduces endogenous production of fat, to balance all the fat the get in their diet.

 

--Dean

[nicholson]

Yes.  Seems inevitable that in any isolated group the small number among them that, with lucky DNA, are better able to bring descendants to maturity in the circumstances in which the group finds itself, will dominate the gene pool in a rather small number of generations.  If all they have to eat is cold water fish and walruses  ........ 

 

I was watching the progress of several families of ducks on a couple of local ponds this summer.  One of them hatched eight chicks and lost only one over subsequent months.  One hatched twelve chicks and seemingly lost none of them.  Another hatched three and lost one.  And a fourth had ten chicks and eventually lost two.  Doesn't seem too difficult to figure out whose DNA will be dominating the gene pool not too far hence.

 

Rodney.

[TomBAvoider]

You're right, Dean, we all have individual genetic profiles, and that certainly has an impact in what the optimal diet is, but of course, it is not the only factor. It's only a matter of time before we all will have to adjust our diets very specifically to our own individual situation. It'll be the death of mass nutrition study recommendations, except as public health research - what applies to 60% of some population, may be exactly wrong for you.

[Ron Put]

On 6/28/2020 at 10:44 AM, TomBAvoider said:

what applies to 60% of some population, may be exactly wrong for you

This has already happened :)

Stuff like lactose intolerance and AMI1 starch digestive enzymes are evolutionary changes prevalent only in certain populations, for instance.  Caffeine fast metabolizers benefit from coffee consumption, while for those who are not, coffee is detrimental.  And so on.

But apart from genetics and epigenetics, the microbiome appears to play an enormous part and the science focussing on it is in its infancy.  And who knows what else we are still to discover.

My guess is we'll get where you predict we'll get, but it will take a while, maybe a long while.  In the meantime, mass nutrition recommendations will still have value for most of us.

Edited June 30, 2020 by Ron Put