Variability in human genome

[alphagruis]

There is now much evidence that human adaptation to different kinds of foods is fairly variable among humans because of different evolutionnary tracks our ancestors went through in different parts of the world.

A nice example seems to be the genes that code for amylases, the enzymes that break starch into useful glucose.

First all humans have several copies of such genes in their genomes and all humans produce amylases in their saliva and pancreas secretion, which makes unescapable the conclusion that starches must have played an important role in our ancestors diet.

Second chimps have definitely less copies than humans which suggests starches were more important for us than other primates.

Third there seems to be a definite correlation between dietery habits and number of copies of amylase genes with statistically hunters having less copies than more heavy starch eaters the variability ranging from a few copies up to 15 copies.

 
http://scienceblogs.com/pharyngula/2008/12/amylase_and_human_evolution.php

[Paleo Donk]

I don't get amylase, as usual. If I put a potato into a bowl and can somehow get enough saliva so that it can take a nice bath in my spit will it breakdown? Even if I crush it up as if it were chewed, would anything happen to it? It just seems amylase doesn't really help all that much to begin with. I realize this wasn't exactly the point of the thread but I've always been curious about naturally occurring amylase implies humans as heavy starch consumers.

[goodsamaritan]

Maybe there were more starchy fruits in the past. 

Bananas are starchy when not fully ripe.

Mabolo fruit are starchy.

jack fruit is starchy and it is an ancient fruit.

[alphagruis]

Maybe there were more starchy fruits in the past. 

Bananas are starchy when not fully ripe.

Mabolo fruit are starchy.

jack fruit is starchy and it is an ancient fruit.

Yes, starch is largely present in all (especially) wild plant foods, in roots or fruits but also in leaves and buds. It is one way for plants to store energy as glycogen is the relevant similar way to store energy for animals. The other way to store energy in both animal and plants kingdoms is fat.

I don't get amylase, as usual. If I put a potato into a bowl and can somehow get enough saliva so that it can take a nice bath in my spit will it breakdown? Even if I crush it up as if it were chewed, would anything happen to it? It just seems amylase doesn't really help all that much to begin with.

Yes doing this experiment i.e. this mixture of saliva and chewed potato indeed shows the progressive release of glucose or other simple sugars readily soluble in water. Starch in contrast is not soluble in water.

[kurite]

There is now much evidence that human adaptation to different kinds of foods is fairly variable among humans because of different evolutionnary tracks our ancestors went through in different parts of the world.
http://scienceblogs.com/pharyngula/2008/12/amylase_and_human_evolution.php

Are you saying that each of us have different abilities of digesting certain foods? If you are, a good example of this is native americans. A portion of their population does not have an enzyme to break down alcohol efficiently and it enters their blood stream much more rapidly.

[PaleoPhil]

From the link: cultures with diets heavy in starch, agricultural populations such as Americans, Europeans, and Japanese, or hunter-gathers who live on many roots and tubers, have a higher average copy number than cultures that depend more on hunting and fishing.

Thanks for the excellent find, Alphagruis. I was just speculating about this possibility at another forum yesterday and have in the past as well. It would explain a lot. Especially if I really do have some NeanderThal genes in me. Both epigenetics and genetics could play a role.

Celtic, Welsh, Scottish and Scandinavian (and I'll bet Arctic Siberian) peoples also tend to have trouble digesting alcohol (http://www.arisealcoholrecovery.com/?page_id=5)--and gluten. This correlates well with the peoples that scientists think have the highest levels of hunter-gatherer genes.

[wodgina]

From the link: cultures with diets heavy in starch, agricultural populations such as Americans, Europeans, and Japanese, or hunter-gathers who live on many roots and tubers, have a higher average copy number than cultures that depend more on hunting and fishing.

Thanks for the excellent find, Alphagruis. I was just speculating about this possibility at another forum yesterday and have in the past as well. It would explain a lot. Especially if I really do have some NeanderThal genes in me. Both epigenetics and genetics could play a role.

Celtic, Welsh, Scottish and Scandinavian (and I'll bet Arctic Siberian) peoples also tend to have trouble digesting alcohol (http://www.arisealcoholrecovery.com/?page_id=5)--and gluten. This correlates well with the peoples that scientists think have the highest levels of hunter-gatherer genes.

Minus the Siberians these peoples also have the highest levels of schizophrenia in the world.

[alphagruis]

Are you saying that each of us have different abilities of digesting certain foods? If you are, a good example of this is native americans. A portion of their population does not have an enzyme to break down alcohol efficiently and it enters their blood stream much more rapidly.

Yes, absolutely, that's the point I wanted to convey.

This means that there is actually nothing like a "universal optimum diet" for all humans. 

[goodsamaritan]

Raw Paleo Diet has enough variation in it.
Ratio of fruit, veg, meat, fat can all be varied according to ones needs.

[alphagruis]

 I agree GS. Within the RPD concept each of us has apparently to find out what's best, in particular how much plant or animal food etc.

These "details" may also change for non genetic reasons, depending on specific period during the lifetime of a given person. For instance the diet may obviously change substantially during pregnancy or breastfeeding. 

[kurite]

Yes although we do need to eat different amounts of plants and meat every humans optimal diet is still raw paleo just in different ratios.

[Raw Kyle]

Yes, absolutely, that's the point I wanted to convey.

This means that there is actually nothing like a "universal optimum diet" for all humans.  

I'd like to pose a counterpoint. Maybe it's digestibility of unhealthy foods that is variable, not long eaten rpd foods. I've never heard of someone not being able to digest meat, and everyone I've seen try raw meat does well on it. However throughout cultures you see different tendencies towards problems on things like dairy, gluten, shellfish, alcohol etc...maybe these foods are just the new foods in different cultures, and the ones that ate them first do better on them, but that doesn't mean they are optimum or need to be included. Again I will say that I have yet to meet someone allergic or otherwise unable to do well eating raw grass fed ruminant meat.

[alphagruis]

Well, I'm not quite sure. Of course, one expects the variability to be more important with respect of neolithic foods than more ancient paleo food.

Yet if one considers the ZC (actually LC) diets promoted by many forumers here, there is a clear-cut variability in our ability to excrete uric acid , one of the waste products generated more abundantly by this diet due to several reasons in particular ketosis.

A series of genes with different more or less efficient variants are indeed known to be involved in the kidney in the excretion
process of uric acid. There are families prone to gout arthritis. Only primates are confronted with this limitation of nitrogen waste excretion, all other mammals and in particular carnivores have an enzyme that converts uric acid into more water soluble allantoin.

This strongly suggest that our adaptation to LC is most likely highly variable too.    

[Paleo Donk]

I've read the liver has a limit of around 400g of protein it can use per day to process into glucose. Now, if humans can limit their protein to just the amount that body needs per day then very little gluconeogenisis is going to occur and thus little uric acid will be produced. Is that correct? So, maybe only the people who consume a high protein diet will have to worry about uric acid being a problem.

Also ZC is actually achievable since muscle meats do contain 0 carbohydrate a day after being slaughtered as all the glycogen has run dry. Since there are those that eat just muscle meats and water, they are technically zero carbers. There do however exist (I think) no ZC animals since all carnivores will eat fresh meat with glycogen or small amounts of vegetation to purge their guts.

I'd actually suspect there to be very little variability with regards to how well humans do with a carnivorous diet if we were fed it from birth. I think the problems and endless variability that comes with handling various low-carb diets is a process of disturbed metabolisms from decades of eating garbage.

[klowcarb]

I'd actually suspect there to be very little variability with regards to how well humans do with a carnivorous diet if we were fed it from birth. I think the problems and endless variability that comes with handling various low-carb diets is a process of disturbed metabolisms from decades of eating garbage.

I agree with this completely.

[alphagruis]

I've read the liver has a limit of around 400g of protein it can use per day to process into glucose. Now, if humans can limit their protein to just the amount that body needs per day then very little gluconeogenisis is going to occur and thus little uric acid will be produced. Is that correct? So, maybe only the people who consume a high protein diet will have to worry about uric acid being a problem.

In ZC the liver necessarily converts part of the appropriate aminoacids from digestion into glucose just because the relevant metabolic pathway becomes active when there is no or little glucose available or in store. That's simple biochemistry logic.

This means that nitrogen containing waste is produced in this process since the glucose molecule does not contain nitrogen and amino acids do.

So if our liver has to produce the irreductible amount of glucose we need from protein rather than receive it directly from diet additional nitrogen containing waste is produced and has to be excreted. I can't see how to escape from this reality and thus the relevance of my remark about the limitation of nitrogen waste excretion in primates as compared to other mammals.

 

Also ZC is actually achievable since muscle meats do contain 0 carbohydrate a day after being slaughtered as all the glycogen has run dry. Since there are those that eat just muscle meats and water, they are technically zero carbers. There do however exist (I think) no ZC animals since all carnivores will eat fresh meat with glycogen or small amounts of vegetation to purge their guts.

First there is not yet any evidence that "ZC" based exclusively on muscle meat and fat from land mammals and water is "achievable" without any health problems over tens of years and a fortiori over a lifetime or several generations. I do not claim that it is not, just that we definitely don't know yet. I also encourage those of us who experiment with this diet to do it. But very cautiously without prelogic ideology. If we don't want to be fooled we have to be open minded and cautious.
 
Second it is still not true that this "ZC" diet is technically zero carb intake even if the meat is eaten after glycogen decay. One reason for instance is that a good deal of the proteins in living system are enzymatically glycated i. e. attached to a specific sugar molecule to be functional. More generally all biological matter contains some carbs, protein, fat etc
  

I'd actually suspect there to be very little variability with regards to how well humans do with a carnivorous diet if we were fed it from birth. I think the problems and endless variability that comes with handling various low-carb diets is a process of disturbed metabolisms from decades of eating garbage.

This kind of variability is not the point I wanted to address in this thread. I agree with you that the tolerance of any diet not just ZC is highly variable depending on our specific "history" of garbage eating.
The variability I speak of is a genetic one related to our limited ability to excrete uric acid and this variability undoubtedly is a well documented reality.  

[Raw Kyle]

The obsession with eating truly "zero carb" is a little silly. I think most reasonable members understand that zero carb refers to consuming no overt carbs. Of course every food in nature has a little bit of carb, fat and protein. But if something is <1% carbs then it makes little to no metabolic difference.

I think the reasonable debate to be having is whether the gluconeogenesis that would have to happen to get your needed carbs is desirable or not against the insulin effect from consuming that amount of carbs directly.

But really when it comes down to it you're not going to be able to measure out the exact amount of protein or carbs you need to keep a certain balance anyway. But you could probably do a pretty good approximation, based on that 400g figure. Anyone know how you could figure out how many carbs an average body uses per day for necessary function?

[alphagruis]

The human brain energy consumption is reported to be about 20% of the total energy consumption of human whole body.

This amounts to roughly .2 X 2400 = 480 kcal / day (or 23 Watts) which corresponds in terms of glucose with 4 kcal/g to roughly 120 g / day

In LC situation half of this can be covered by ketone bodies so that the irreductible quantity of glucose seems to be roughly 60 g / day. I don't know precisely what this rough estimation is worth.

At any rate either this glucose comes from diet ( for instance about 300 g potatoes or 90 g of honey ) or it is essentially produced by liver and kidney from amino acids. The liver can easily produce that much.

 

[Paleo Donk]

In ZC the liver necessarily converts part of the appropriate aminoacids from digestion into glucose just because the relevant metabolic pathway becomes active when there is no or little glucose available or in store. That's simple biochemistry logic.

This means that nitrogen containing waste is produced in this process since the glucose molecule does not contain nitrogen and amino acids do.

So if our liver has to produce the irreductible amount of glucose we need from protein rather than receive it directly from diet additional nitrogen containing waste is produced and has to be excreted. I can't see how to escape from this reality and thus the relevance of my remark about the limitation of nitrogen waste excretion in primates as compared to other mammals.

I don think I agree with you that during ZC, the liver necessarily converts amino acids to glucose or that there is this "irreductible" amount of glucose needed. Or perhaps there is just very little conversion. I'm not sure if it has ever been empirically measured how much gluconeogenesis is occurring during ZC, especially for those adapted after several months of ZC. From your last post, you are admitting that you don't know how much glucose is actually needed for the brain during LC. What exact areas in the brain require glucose and definitely cannot get their energy from ketones? What cells do not possess mitochondria? If all brain cells do, could the brains requirement for glucose be close to 0?

In fasting studies after about 2 weeks, well past the point where carbohydrates have all been used up, the body consumes about 50g of its own muscle tissue and 130g of fat totaling around 1400 calories. This should give us an absolute minimum for the amount of glucose that can be used to sustain life. I've read that 10% of fat molecules will convert to glucose from the glycerol. Maybe thats all the glucose we need. I'm not sure how much of the 50g of protein is used to repair tissue but I would guess its almost all of it. I don't see why the body would go through the extra trouble to convert any amino acids in starvation mode to glucose as this is a destructive process and takes 10-11 ATP to complete (about 30% of what 1 gram of glucose gives). I think there are very few cells that are solely dependent on glucose (red blood cells are the only ones?)

First there is not yet any evidence that "ZC" based exclusively on muscle meat and fat from land mammals and water is "achievable" without any health problems over tens of years and a fortiori over a lifetime or several generations. I do not claim that it is not, just thatwe definitely don't know yet. I also encourage those of us who experiment with this diet to do it. But very cautiously without prelogic ideology. If we don't want to be fooled we have to be open minded and cautious.

I agree with you completely that there is no data out there that ZC can sustain good health over decades and the people in good health now tell us only one small step of the process. At the same time, there are no recent accounts of humans eating entirely raw for decades at a time with good health.

The variability I speak of is a genetic one related to our limited ability to excrete uric acid and this variability undoubtedly is a well documented reality.

How limited are you talking about? I have a theory that the body will adapt to almost any level of carb intake, in that it will use proportionally the amount of carbs that we consume. Its systems will be fine tuned to using whatever inputs we give it. Thus for ZC, almost all components in the body will be running on fat and ketones and with vegans, they will be "efficiently" run on glucose. There is an exception here though, and thats when we consume too much protein. I believe the body will convert all excess amino acids after its done using it for repair to glucose. Perhaps too many amino acids in the blood are dangerous. I suspect the body knows what its doing. But, if we keep protein to levels that take care of basic repair, the amount of gluconeogenisis should be limited. To take it to the extreme, if protein consumption is less than what the body needs for repair then there should be almost exactly 0 gluconeogenesis, as I would imagine repair to be more important than a process of getting energy destructively, when you can use fat and glycerol easier.

[alphagruis]

The limitation I had in mind is in the amount of nitrogen waste products we as a primate can excrete easily when compared to other mammals and in particular carnivores.

Besides, I agree with you that we are probably easily capable to adapt to a highly variable amount of carbohydrates in our diet.

As to the absence of evidence with respect to the validity of an absolutely raw diet over decades, I also agree completely.

As to the irreductible amount of glucose we need my 60g / day are of course just a very rough estimate. Might be substantially less but I doubt that it is "close to zero". The reason I'm reluctant is that whatever we eat our organism does whatever is possible to maintain the glucose concentration in blood close to about .90-1.0 g/l. I don't know in every respect why nature does so but the reason must be fairly important since this is a general feature in mammals and probably other animals and costs a lot of energy if the glucose has to be obtained from protein. And the relevant glucose must be obtained in some way, if not from diet it must be obtained by gluconeogenesis.

As to the presence of mitochondria, neurons possess these very important organelles and aerobic complete glucose oxidation as it clearly takes place in brain needs their presence anyway.

Some interesting info in this respect here

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=bnchm&part=A2213

The brain utilizes ketones in states of ketosis

In special circumstances, the brain may fulfill its nutritional needs partly, although not completely, with substrates other than glucose. Normally, there are no significant cerebral arteriovenous differences for d-?-hydroxybutyrate and acetoacetate, which are “ketone bodies” formed in the course of the catabolism of fatty acids by liver. Owen and coworkers [26] observed, however, that when human patients were treated for severe obesity by complete fasting for several weeks, there was considerable uptake of both substances by the brain. If one assumed that the substances were oxidized completely, their rates of utilization would have accounted for more than 50% of the total cerebral oxygen consumption, more than that accounted for by the glucose uptake. d-?-hydroxybutyrate uptake was several times greater than that of acetoacetate, a reflection of its higher concentration in the blood. The enzymes responsible for their metabolism, d-?-hydroxybutyrate dehydrogenase, acetoacetate-succinyl-CoA transferase and acetoacetyl-CoA-thiolase, are present in brain tissue in sufficient amounts to convert them into acyl-CoA and to feed them into the tricarboxylic acid cycle at a sufficient rate to satisfy the metabolic demands of the brain [27].

Under normal circumstances, that is, ample glucose and few ketone bodies in the blood, the brain apparently does not oxidize ketones in any significant amounts. In prolonged starvation, the carbohydrate stores of the body are exhausted and the rate of gluconeogenesis is insufficient to provide glucose fast enough to meet the requirements of the brain; blood ketone concentrations rise as a result of the rapid fat catabolism. The brain then apparently turns to the ketone bodies as the source of its energy supply.

Cerebral utilization of ketone bodies appears to follow passively their concentrations in arterial blood [27]. In normal adults, ketone concentrations are very low in blood and cerebral utilization of ketones is negligible. In ketotic states resulting from starvation; fat-feeding or ketogenic diets; diabetes; or any other condition that accelerates the mobilization and catabolism of fat, cerebral utilization of ketones is increased more or less in direct proportion to the degree of ketosis [27]. Significant utilization of ketone bodies by the brain is, however, normal in the neonatal period. The newborn infant tends to be hypoglycemic but becomes ketotic when it begins to nurse because of the high fat content of the mother's milk. When weaned onto the normal, relatively high-carbohydrate diet, the ketosis and cerebral ketone utilization disappear. Studies have been carried out mainly in the infant rat, but there is evidence that the situation is similar in the human infant.

The first two enzymes in the pathway of ketone utilization are d-?-hydroxybutyrate dehydrogenase and acetoacetyl-succinyl-CoA transferase. These exhibit a postnatal pattern of development that is well adapted to the nutritional demands of the brain. At birth, the activity of these enzymes in the brain is low; activity rises rapidly with the ketosis that develops with the onset of suckling, reaches its peak just before weaning and then gradually declines after weaning to normal adult rates of approximately one-third to one-fourth the maximal rates attained [27,28].

It should be noted that d-?-hydroxybutyrate is incapable of maintaining or restoring normal cerebral function in the absence of glucose in the blood. This suggests that, although it can partially replace glucose, it cannot fully satisfy the cerebral energy needs in the absence of some glucose consumption. One explanation may be that the first product of d-?-hydroxybutyrate oxidation, acetoacetate, is metabolized further by its displacement of the succinyl moiety of succinyl-CoA to form acetoacetyl-CoA. A certain rate of glucose utilization may be essential to drive the tricarboxylic cycle, to provide enough succinyl-CoA to permit the further oxidation of acetoacetate and, hence, to pull along the oxidation of d-?-hydroxybutyrate.

 

[Paleo Donk]

Ho hum, this thread just got much more exciting. Thanks alpha for mentioning the relatively poor ability for primates to handle nitrogen waste and the possible need for glucose in the brain during starvation. I don't think the level is near zero anymore and your 60g estimate might be much closer to the truth.

I am looking but have yet to find what is the minimum amount of protein that body needs to repair all itself. On dirty carnivore, there is a thread  that mentions that olympic lifters maintained positive nitrogen balance while getting just 30g of protein a day. If this is true, then this is huge! I quoted that during starvation 50g of skeletal muscle are broken down. I assumed this was all for repair. The bear also mentioned that one needs just 30g of protein a day to build muscle. Maybe much of the 50g/day of protein during starvation is actually used for glucose to fuel the brain??!! It looks like this could easily be the case.

Also, if lots of people here are experiencing bubbly urine, this could be a sign of excess protein intake.

I also found a good little study done on malliard products and nitrogen waste with conclusions here.

Compared with consumption of the WD, consumption of the BD resulted in 47% higher fecal nitrogen fecal excretion (P = 0.002), 12% lower apparent nitrogen absorption (P = 0.000), and a 6% lower nitrogen digestibility (P = 0.000).

So, it seems the body is less efficient when it comes to handling cooked proteins and to me it points to the fact that these cooked proteins are used more for energy and not for repair. So, for raw animal foodists, the protein needed will be even less as more if it will go for repair than energy.

This all seems to make so much sense and fall more in line with us being scavengers as opposed to hunters for a much longer period of time. If we are more adapted to scavenging then we should do much better on low-protein diets as there is little protein to be had as a scavenger. This fits into the bone marrow, brains and whatever vegetation we could gather path.

So, with all this, I am going to experiment with eating around 50g of protein a day with the rest being fat, though now this brings up a huge question mark about how much vegetation to add in. If my brain was infact needing this glucose produced from excessive protein then it would make sense to supply at least some it from diet. Even though fat will provide some glucose, I don't think it will make up for all the glucose provided from the extra protein. I am also going to be lifting heavy twice a week and so I should get some interesting results, hopefully pretty soon.