Genes And PUFA

[lvysaur]

http://2.bp.blogspot.com/-9faAor2hsHU/VQTCpkYlwdI/AAAAAAAAKAY/66NrPHxDoJ4/s1600/change.jpg

Graph A on that image shows the prevalence of various alleles in the population of Europe with respect to time.

One notable feature is LCT allele, which is associated with lactose tolerance.

Another very notable feature that doesn't get talked about a lot in the popsci press is the FADS1 gene evolution (colored in grey). We see that the prevalence of the derived allele goes from 0 to 60%.

rs174546 - SNPedia

Here we see that the derived allele has a rough correlation with climatic origin. The derived allele (which causes high cholesterol on a high PUFA diet) is very high in west Africans, east Africans, the Maasai, and Gujurati Indians. Allele frequency is about 90%.

In Europeans and North Asians, the allele frequency is about 60%.

And of course, in the indigenous Europeans of 8,000 years ago (who probably depended a lot on cold climate fish and game), the allele frequency was about 0%.

Human genome shaped by vegetarian diet increases risk of cancer and heart disease

A separate SNP, associated with increased arachidonic acid synthesis from lineoleate, is higher in populations from India and Africa than from North Asia, Europe, and South America.

And of course, the politically correct headline on that article concerns itself with vegetarianism, and not with excess PUFA consumption, lmao .

 

[tyw]

@m_arch , this is related to the point which you mentioned here, and which I didn't give much follow-up to -- https://raypeatforum.com/community/threads/haiduts-summary-of-pufa.7619/page-3#post-184333

This is some evidence to suggest that people of more extreme Northern (or Southern) Latitudes have less expression of the Fatty Acid Desaturase enzymes (which is what 'FADS' stands for). Less FADS activity means "less conversion of saturated fat to unsaturated fat".

Implications are that those people with high activity in these genes probably can (and should) eat a much lower PUFA diet, and in general, can get away with eating less fat without any side effects. ie: They will make all the needed essentially fatty acids from the small amounts of fat that they consume. We can speculate that this is due to a low amount of unsaturated fats in the environment in which these groups evolved under.

It is then hypothesised that as you go further away from the Equator, natural adaptations in flora and fauna increase Unsaturated Fatty acid content (to deal with cold and lack of light), and this would end up in the diets of humans, who then down-regulated Desaturase activity in the face of enough dietary unsaturated fatty acids.

For people hailing from such ancestry, they may experience the same issues as m_arch on low fat, and should probably not use very low fat diets.

....

 

[m_arch]

@tyw yeah it makes sense. Observationally a lot of populations hailing from equatorial ancestry seem to get fat very easily following a western pufa-laiden diet.

@Ivysaur awesome graph!

 

[lvysaur]

These are still just allele frequencies. The true test for the individual is what the individual genotype is.

 

[tyw]

These are still just allele frequencies. The true test for the individual is what the individual genotype is.

This is correct, and the likelihoods given are just population averages.

One can then get their actual alleles using a genomics test. eg: my 23andme gene analysis says that I have a 'CT' genotype for both rs174570 and rs174546. The 'C' allele is said to be the one associated with more eager desaturase activity.

Note that some papers will say something like, "The T allele was associated with higher LA concentrations and lower ARA concentrations". Same thing. ARA (arachidonic acid / 20:4) is more unsaturated than LA (linoleic acid / 18:2), which means "lower unsaturation with T allele" or what I prefer to say: "More unsaturation with C allele".​

----

Now to talk about a separate but related topic -- to address the general distaste for "genetics".

I have been critical of using genetic analyses to infer high level disease conditions (like Heart Disease), because such diseases are borne of chronic stressors that work on all levels of the hierarchy of the organism.

IMO, Genetic analysis is ONLY useful for low level mechanics, involving specific protein expression and/or enzymatic pathways.

Some of these low level mechanics may have significant high level effects. eg: SNPs governing melatonin production really affect sleep on a very acute basis. Most genetic expression however, are only significant when contingent upon higher level mechanisms.

In this case, we can assume that people with the 'C' allele in the stated genes will likely be able to produce endogenous PUFA more readily. What high level effects this will have, is still contingent upon factors like existing dietary intake, immune system stress, etc ....

In this case (of desaturase activity), it is more useful to experiment with different macronutrient intakes, rather than rely on genomic analysis. In other cases, genomic analysis can be very useful.

.....

 

[Luann]

@m_archLess FADS activity means "less conversion of saturated fat to unsaturated fat".
....

Note that humans can synthesize mono- from saturated fat, but not PUFA from mono.

 

[tyw]

Note that humans can synthesize mono- from saturated fat, but not PUFA from mono.

Error on my part Delta-9 desaturases are the enzymes that is responsible for desaturating saturated fatty acids.

The delta-5 desaturases that are governed by the FASD-1 gene is more responsible for desaturating PUFAs, as per these pathways:

Source: Essential Fatty Acids​

It is then generally accepted that we can't really produce 18:2 and 18:3, but if these are present, then the rest of the PUFAs can be synthesised. Reference study -- De novo lipogenesis in the differentiating human adipocyte can provide all fatty acids necessary for maturation

Some degree of these HUFAs (highly unsaturated fatty acids) are necessary, and people with "less eager desaturase genotypes" will not be able to synthesise enough of these HUFAs from a small pool of 18:2 and 18:3. Those people will probably do better with getting some of those HUFAs directly through the diet.

Note that we're still talking fairly low amounts here .... eg: just 2 eggs will probably net you 10g fat, and of that, 1.5g linolenic acid (18:2), and depending on the feed of the chickens, probably a good deal of Arachidonic Acid and even EPA and DHA too. This is IMO, enough daily PUFA for most people.

Now, there's a big difference between doing that, and going extremely low fat, and only getting 18:2 and 18:3, with none of the HUFAs from diet. While there is going to the 18:2 and 18:3 in basically any whole food (even coconut oil), the inefficiency of conversion will lead to deficiency of HUFA in some people, and yet yield perfectly adequate quantities in others.

Such very low fat diets have been documented in equatorial populations (Okinawa, Thailand, etc), and I do not think that non-equatorial populations will fare well on such diets. ie: Those 2 eggs a day may be necessary for some people to maintain good health.

Sidenote: I've stated before (I forget where ...), that people put on Therapeutic Very-Low-Fat diets (like the Kempner Rice Diet) generally had significant body fat to lose. ie: They were using the PUFAs that they had already stored over their lifetimes -- their cells were "eating a high PUFA diet" by mobilising existing PUFAs.​

Of course, we are talking about extremes in the macro-nutrient scale here. But given some existing sentiment toward "cutting PUFAs at all costs", I generally would like to say, "Chill mate , don't worry too much about eating some small amount of PUFAs."

Instead, worry about keeping body composition good -- https://raypeatforum.com/community/...-without-weight-gain.10163/page-3#post-178858​

.....

 

[Giraffe]

Note that humans can synthesize mono- from saturated fat, but not PUFA from mono.

Why do you think so?

Mead acid - Wikipedia

Under severe conditions of essential fatty acid deprivation, mammals will elongate and desaturate oleic acid to make mead acid, (20:3, n−9).This has been documented to a lesser extent in vegetarians and semi-vegetarians following an unbalanced diet.

 

[Luann]

@Giraffe, yes, Mead acid. But otherwise we don't have what in plants is called FAD2 the desaturase at delta-12 and -15, the oleic desaturase.

 

[lvysaur]

rs174546 - SNPedia

Here we see that the derived allele has a rough correlation with climatic origin. The derived allele (which causes high cholesterol on a high PUFA diet) is very high in west Africans, east Africans, the Maasai, and Gujurati Indians. Allele frequency is about 90%.

I'm going to update this to say that what I originally said was misleading.

ALFRED Site graphing information

Very low frequencies of the C allele (high blood cholesterol while eating PUFA) can be found in many of the diverse equatorial populations listed.

So it's not as simple as "cold climate, more PUFA, low cholesterol while eating PUFA".

I couldn't find any further info on the desaturase SNP though.

 

[Drareg]

I'm going to update this to say that what I originally said was misleading.

ALFRED Site graphing information

Very low frequencies of the C allele (high blood cholesterol while eating PUFA) can be found in many of the diverse equatorial populations listed.

So it's not as simple as "cold climate, more PUFA, low cholesterol while eating PUFA".

I couldn't find any further info on the desaturase SNP though.

Great find.
Using 23 and me as a tool is quite good,I wouldn't view the resits of your genes as static,I think the argumnet remains that an adaption like this is very much epigenetic.
If we have a more dynamic method in the future of testing genes like the illuminia device which is like a USB card of sort,we could then gets daily and see what's expressing itself under certain conditions and foods consumed.
It's all seems to be heading in this direction.

It's also plausible that the they needed to hibernate in the early days after migration?

 

[Drareg]

This is correct, and the likelihoods given are just population averages.

One can then get their actual alleles using a genomics test. eg: my 23andme gene analysis says that I have a 'CT' genotype for both rs174570 and rs174546. The 'C' allele is said to be the one associated with more eager desaturase activity.

Note that some papers will say something like, "The T allele was associated with higher LA concentrations and lower ARA concentrations". Same thing. ARA (arachidonic acid / 20:4) is more unsaturated than LA (linoleic acid / 18:2), which means "lower unsaturation with T allele" or what I prefer to say: "More unsaturation with C allele".​

----

Now to talk about a separate but related topic -- to address the general distaste for "genetics".

I have been critical of using genetic analyses to infer high level disease conditions (like Heart Disease), because such diseases are borne of chronic stressors that work on all levels of the hierarchy of the organism.

IMO, Genetic analysis is ONLY useful for low level mechanics, involving specific protein expression and/or enzymatic pathways.

Some of these low level mechanics may have significant high level effects. eg: SNPs governing melatonin production really affect sleep on a very acute basis. Most genetic expression however, are only significant when contingent upon higher level mechanisms.

In this case, we can assume that people with the 'C' allele in the stated genes will likely be able to produce endogenous PUFA more readily. What high level effects this will have, is still contingent upon factors like existing dietary intake, immune system stress, etc ....

In this case (of desaturase activity), it is more useful to experiment with different macronutrient intakes, rather than rely on genomic analysis. In other cases, genomic analysis can be very useful.

.....

I think the overall point is genetics is a small piece of the picture for overall health as Peat has mentioned somethings are not coded but we still exist. For example There is no code for making magnesium and other minerals so the outside environment is needed.
I think most people are ok with the term genetics if they acknowledge Epigentics and its workings, melatonin could still changed by epigentic process.

 

[tyw]

I'm going to update this to say that what I originally said was misleading.

ALFRED Site graphing information

Very low frequencies of the C allele (high blood cholesterol while eating PUFA) can be found in many of the diverse equatorial populations listed.

So it's not as simple as "cold climate, more PUFA, low cholesterol while eating PUFA".

I couldn't find any further info on the desaturase SNP though.

Probably has more to do with ancestral prevalence of PUFAs and subsequent consumption in the diet of said populations. This is multi-factorial, and would not just vary according to temperature and latitude.

eg: a population living next to a sea at moderate latitute, and with high levels of fish consumption (which is a common environment in African), vs a land-locked region at moderate latitude.

I think the overall point is genetics is a small piece of the picture for overall health as Peat has mentioned somethings are not coded but we still exist. For example There is no code for making magnesium and other minerals so the outside environment is needed.
I think most people are ok with the term genetics if they acknowledge Epigentics and its workings, melatonin could still changed by epigentic process.

Depends. I judge every mechanism on a case by case basis.

In general, genetic expression has more and more significant impact the lower level we look at. Once we are dealing with centenarian associated FOXO genes, we are talking significantly lower ROS production, where "significant" means that there is a large impact on longevity, regardless of whatever these people do. Doesn't matter if they smoke cigarettes or eat tons of PUFA, their mitochondria don't take on the highly-peroxidation prone high-PUFA phenotype that us other humans would take on if we ate similar levels of PUFA.

The same argument applies to birds, and in my 'PUFA and Birds' articles, I cite studies showing basically no change in bird mitochondrial PUFA concentration despite widely varying dietary PUFA intakes. In other words, bird genes decide that mitochondria should be low PUFA.​

Then, there are some genetic defects that matter, and others that don't, and everything in between. This isn't a question about whether epigenetics is important (of course it is), the question is: "What inherent deficits are an individual burdened with, solely because of their genes".

I obviously won't name the patient, but there was this kid who inherited both an ASMT and a VDR SNP that made it such that dopamine and melatonin production were shut down dramatically. Sleep was poor and stunted growth was a result. Years of investigation required to finally stumble upon a genetic analysis that revealed these defects. Low dose Supplemental melatonin fixed ALL issues (present day is many months after initial treatment, results continue to be good).

NOTE: "fixed all issues" means that this was the weak link that affected all downstream issues that this person faced. It doesn't mean that:

(a) melatonin was all that was required
(b) that the fix would hold for a long time

Constant tweaking needed to be done, but now that a weak link causing a fundamental imbalance is found, it can be treated appropriately, and further tonification of the system can proceed. Else, nothing can proceed, and the patient stays sick.​

This is clearly a case where genes were the main blocking agent to recovery. Will this person be able to overcome the need for exogenous melatonin? Probably in a couple of years of good care and appropriate supplemental and nutritional support.

Melatonin production will probably always be (genetically) lower than someone who didn't have these SNPs, but with enough attention to detail in health protocols, such people may stand a chance at making enough melatonin. They will of course be inherently more fragile, in the sense that say they have to be "80% on point with health protocols" in order to get good sleep, vs "40% on point" in someone who doesn't have these issues. There is no doubt that their genes restrict them to certain limits.

The same applies to other SNPs with obvious detrimental effects. Small changes in low level metabolism can be the agent that blocks all further progress from happening. eg: MTHFR SNPs have been over-emphasised in the past few years now, but in those people who actually have issues there, getting over the initial block, and establishing a healthy-enough baseline (enough to stand a fighting chance at recovery), requires large exogenous support. We're sometimes talking 30mg of 5-MTHF a day, on top of Lithium and what not as a short term protocol, after which transition to addressing other issues can continue.

Genetics: They matter when they matter -- enough to guarantee destruction or salvation. And when they don't matter, they really don't matter .

.....

 

[Drareg]

Depends. I judge every mechanism on a case by case basis.

In general, genetic expression has more and more significant impact the lower level we look at. Once we are dealing with centenarian associated FOXO genes, we are talking significantly lower ROS production, where "significant" means that there is a large impact on longevity, regardless of whatever these people do. Doesn't matter if they smoke cigarettes or eat tons of PUFA, their mitochondria don't take on the highly-peroxidation prone high-PUFA phenotype that us other humans would take on if we ate similar levels of PUFA.

The same argument applies to birds, and in my 'PUFA and Birds' articles, I cite studies showing basically no change in bird mitochondrial PUFA concentration despite widely varying dietary PUFA intakes. In other words, bird genes decide that mitochondria should be low PUFA.​

Then, there are some genetic defects that matter, and others that don't, and everything in between. This isn't a question about whether epigenetics is important (of course it is), the question is: "What inherent deficits are an individual burdened with, solely because of their genes".

I obviously won't name the patient, but there was this kid who inherited both an ASMT and a VDR SNP that made it such that dopamine and melatonin production were shut down dramatically. Sleep was poor and stunted growth was a result. Years of investigation required to finally stumble upon a genetic analysis that revealed these defects. Low dose Supplemental melatonin fixed ALL issues (present day is many months after initial treatment, results continue to be good).

This is clearly a case where genes were the main blocking agent to recovery. Will this person be able to overcome the need for exogenous melatonin? Probably in a couple of years of good care and appropriate supplemental and nutritional support.

Melatonin production will probably always be (genetically) lower than someone who didn't have these SNPs, but with enough attention to detail in health protocols, such people may stand a chance at making enough melatonin. They will of course be inherently more fragile, in the sense that say they have to be "80% on point with health protocols" in order to get good sleep, vs "40% on point" in someone who doesn't have these issues. There is no doubt that their genes restrict them to certain limits.

The same applies to other SNPs with obvious detrimental effects. Small changes in low level metabolism can be the agent that blocks all further progress from happening. eg: MTHFR SNPs have been over-emphasised in the past few years now, but in those people who actually have issues there, getting over the initial block, and establishing a healthy-enough baseline (enough to stand a fighting chance at recovery), requires large exogenous support. We're sometimes talking 30mg of 5-MTHF a day, on top of Lithium and what not as a short term protocol, after which transition to addressing other issues can continue.

Genetics: They matter when they matter -- enough to guarantee destruction or salvation. And when they don't matter, they really don't matter .

.....

It can matter what they do though,if they become magnesium deficient for example,this will effect longevity,the context of ROS production is crucial.
If the mineral and vitamins are getting into the system in required amounts they are pushing forward with their strengths inherited from parents,mess with their food supply and we will get some drama,animals are pretty consistent with their diet,their lives revolve around getting food,humans however follow popular fad diets,food cultures in some area can be considered fad diets,it's unlikely we will find chimps or mice offering dietary advice to other chimps and mice,although humans Change these diets for chimps in captivity causing all sorts of issues,lol.

Melatonin being a hormone is coded so being deficient in magnesium will also effect its expression,deficient in any mineral or vital-amine essential will. At what point or cascade the magnesium deficiency start the drama is extremely difficult to decipher.

It's all very exciting if illumina mass produce a epigentic device that can test as you sit in front of your computer and give dynamic results daily/hourly unfortunately it can't tell us with certainty why certain genes are being expressed,we have a lot more work here.
Sunlight at the equator is also quite telling in relation to the Adaptations mentioned.

Also the torpor/hibernation factor of different hemispheres in the past is interesting in relation to PUFA,these birds you mention like hummingbirds need to go into essentially hibernation at night to survive.

The initial block is crucial,if people don't commit fully like neglecting sunlight or maintaining an aspect of the diet unchanged their inherited weaknesses from parents will stay the same,same applies to stressful jobs,stressful aspect of parenting for example,if you don't Change it or how you perceive it there will be issues.

It's like the gene is untrusting of a minor change,it needs full support to express itself,it's needs to see consistency ,just as we see at the macro level in human behaviour,you need to be a consistent parent to your genes to see the patterns change .

We should test the hypothesis with another thread on those who have done 23 and me to see if the expression make sense in relation to current and past living areas.

 

[Drareg]

My 23 and me results tell me-
CT -rs174546
CC-rs174570
In relation to my descent according to 23 and me I'm predominately North west European,I've never been near the equator but not at extreme latitudes either.

What pills do I take to transform myself?

 

[Drareg]

Does anybody else have their 23 and me results for the above snp's and also your heritage for research purposes within this thread?
This could be a pivotal thread on the forum.

 

[Parsifal]

Does anybody else have their 23 and me results for the above snp's and also your heritage for research purposes within this thread?
This could be a pivotal thread on the forum.

I have my raw data and tried to interpret them in Livewello but never understood how to do it and never really took the time to explore it.

 

[Luann]

This Birds and PUFA study (anyone have a link?) does not show that diet has no effect on mitochondria unless it tested out a diet restricted to mono- and saturated fats. Remember that any poly-unsaturated fatty acid can be further unsaturated if the cell sees fit.

 

[A. squamosa]

check out the book "Beyond Biotechnology" by Craig Holdrege and Steve Talbott if you're interested in genes. Fascinating stuff! So much we don't know.

 

[Drareg]

This Birds and PUFA study (anyone have a link?) does not show that diet has no effect on mitochondria unless it tested out a diet restricted to mono- and saturated fats. Remember that any poly-unsaturated fatty acid can be further unsaturated if the cell sees fit.

No don't have the link can you expand on this in relation to the snp's.