Protein needs and Ketogenic Diet ( was zum Nachdenken)

Hallo, habe zwei sehr interessante Artikel gefunden. Wer Zeit zum Lesen hat sollte das tun.

1 ARTIKEL:

Protein for Athletes
How much protein should athletes consume?

There are a few magic numbers for protein intake that we want to be aware of:

Nitrogen balance. Nitrogen comes into the body in dietary protein and leaves the body in urine as ammonia, urea, and uric acid after proteins are metabolized. So when a person is in nitrogen balance, the amount of dietary protein matches the amount of metabolized protein, and the protein content of the body is unchanged. Very likely, the muscle content is unchanged too.
Exhaustion of benefits. We want to find the “plateau region” for nutrients. Athletes want to know: at what level of protein intake does protein no longer help build muscle?
Toxicity. At what level of protein intake does protein begin to damage health?


There’s a great deal of variability across persons. Some people are in nitrogen balance at protein intake of 0.9 g/kg/day; others need as much as 1.5 g/kg/day. At 1.2 g/kg/day, half the sample was in nitrogen balance.

Various factors influence the interpretation of this data:

The sample was of endurance athletes. Endurance exercise increases protein needs, so most people would reach nitrogen balance at lower protein intakes. Resistance exercise doesn’t require as much protein: Experienced bodybuilders are typically in nitrogen balance at 1.2 g/kg/day. [2]
Most of the sample probably ate a high-carb diet. Glucose needs were met from dietary carbohydrates. Low-carb dieters would need additional protein for glucose manufacture.
As Ned states, in caloric deficit, protein needs are increased; in caloric surplus, protein needs are decreased. If you’re restricting calories for weight loss, expect to need a bit more protein to avoid muscle loss.
Supplementing leucine “increased protein synthesis and decreased protein breakdown” [2], thus leading to nitrogen balance at lower protein intakes.
The point of nitrogen balance is dynamic: if everyone in the sample ate 0.9 g/kg/day, then they’d eventually get into nitrogen balance at 0.9 g/kg/day. The body adjusts to conserve muscle at given food availability.

The average person needs much less protein to be in nitrogen balance. The US RDA for protein, 0.8 g/kg/day, was set so that 97.5% of Americans would be in nitrogen balance. [2] But just to be conservative, and because we’re developing advice for athletes, let’s consider 1.5 g/kg/day as the protein intake that brings our athletes into nitrogen balance.

What about the protein intake that exhausts benefits? At what intake is muscle synthesis no longer promoted?

Ned, offers the following answer: “[P]rotein intake beyond 25 percent of what is necessary to achieve a nitrogen balance of zero would have no effect on muscle gain.”

On my reading it’s not so easy to infer a clear answer, but let’s go with this. If so, then muscle gains would be exhausted at 1.25*1.5 = 1.875 g/kg/day even for the most strenuous athletes.

What about toxicity?

At a protein intake of 230 g/day (920 calories), the body’s ability to convert ammonia to urea is saturated. [3] This means the nitrogen from every additional gram of protein lingers in the body as ammonia, a toxin.


Let’s say our athlete is an 80 kg man. Then maximum muscle gain will be achieved at a protein intake of 1.875*80 = 150 g/day. Toxicity will begin somewhere between 150 to 200 g/day. So the “plateau region” where all the benefits, and none of the toxicity, are achieved is between 150 g/day and some protein intake not much above 150 g/day.

The plateau region is quite narrow! What this tells us is that athletes should consume about 150 g/day protein.

This assumes a high-carb diet, so that no protein is needed for gluconeogenesis. The body utilizes about 600 calories/day of glucose, plus another 100 calories per hour of intense training.

With carb intakes below 600 calories/day, additional dietary protein would be needed, because protein would be consumed nearly 1-for-1 with the missing carbs.

So we can summarize these results as follows:

On a high-carb diet (>600 calories/day), 600 protein calories/day maximizes muscle gain.
On a low-carb diet (<600 calories/day), 1200 carb+protein calories/day maximizes muscle gain.

Looking back at Advocatus Avocado’s personal experience, he eats a low-carb diet with 460 carb calories per day. We predict therefore that he would need 740 protein calories a day to maximize his muscle gain (plus up to another 100 calories per hour of training, to replace lost glycogen).

Advocatus says he needs 800 protein calories/day to maximize muscle gain. Close enough for blog work!

At these protein intake levels, Advocatus is probably experiencing mild ammonia toxicity. He might slightly improve his health by eating a few more carbs, and cutting his protein intake a bit.

He might also find that leucine supplementation would reduce his protein needs a bit.

Those who are content with maintaining an ordinary person’s muscle mass can get by with relatively low protein intakes of 0.8 g/kg/day or less. But muscle-building athletes need high protein intakes, around 1.9 g/kg/day, to maximize the rate of muscle gain. If they eat low-carb, they may need even more protein. Such high protein intakes are likely to exceed the threshold of toxicity.


2 ARTIKEL
Ketogenic Diets :

Preventing Muscle and Bone Loss on Ketogenic Diets
Filed under: Ketogenic Diet

We’re in the midst of a series exploring therapeutic ketogenic diets. Our immediate goal is to help the NBIA kids, Zach and Matthias, but most of the ideas will be transferable to other conditions – and even to healthy people who engage in occasional or intermittent ketogenic dieting for disease prevention.

First, some data. A review of childhood epilepsy patients on ketogenic diets prescribed by Johns Hopkins Hospital doctors points out problems experienced by the children:

Weak bones. Skeletal fractures occurred in 6 of 28 children following the ketogenic diet for 6 years; 4 children had fractures at separate locations and times. [1]
Stunted growth. By the end of the 6 years, 23 of the 28 children were in the bottom tenth by height of their age group. [1]

Other negative effects highlighted in the review include kidney stones (7 children developed stones) and dyslipidemia (total cholesterol as high as 383 mg/dl). [1] As we’ve discussed in previous posts, these are probably caused by malnutrition. Kidney stones are usually due to deficiency of antioxidants; dyslipidemia due to deficiency of minerals, vitamins, or choline.

It’s a little hard to nail down the exact cause of the bone fractures and stunted growth because the diets were so atrocious.

First, children were told to eat calorically restricted diets to invoke the starvation response:

Calories were restricted to 75% of estimated daily needs, and fluids were calculated at 80% of daily requirements. [1]

Second, some of the children were fed formula – not real food:

[C]hildren fed only with formula all received a combination of Ross Carbohydrate-Free, Mead Johnson Microlipid, and Ross Polycose formulas to provide a nutritionally complete diet … [1]

For those keeping score, Ross Carbohydrate Free consists of soy protein isolate, high oleic safflower oil, soy oil, and coconut oil, plus vitamins and minerals. Microlipid is a safflower oil emulsion. Ross Polycose is hydrolyzed cornstarch.

There are two problems with this diet design. First, purified diets are notoriously unhealthy; they are missing all kinds of helpful compounds found in real food. Animals do poorly on such diets, as Chris Masterjohn recently noted. Chris quotes the American Institute of Nutrition:

Purified diets without added ultratrace elements support growth and reproduction, but investigators have noted that animals exposed to stress, toxins, carcinogens or diet imbalances display more negative effects when fed purified diets than when fed cereal-based diets.

The second problem, from my point of view, is that they made little use of short-chain fats and ketogenic amino acids to make the diet ketogenic. Instead, they relied on protein and carb restriction and overall calorie restriction to force ketone production. In short, they intentionally starved the kids.

Obviously, starvation tends to produce stunted growth; this is why North Koreans are shorter than South Koreans.

I believe such starvation is totally unnecessary. Use of short-chain fats and ketogenic amino acids can trigger high ketone production even on a nourishing diet.

Nevertheless, even an awful diet is better than the best pharmaceutical drugs:

All of the parents interviewed preferred the diet over medications; 12 cited fewer side effects (such as cognitive dulling, sedation, ataxia, and behavioral problems) from medications that were successfully discontinued, and 11 cited decreased seizure frequency over medications as their primary reason. [1]

Muscle Loss

Another, closely related, problem on ketogenic diets is loss of muscle. You don’t often see bodybuilders or Olympic weight lifters who eat a continuously ketogenic diet. It can be hard to add muscle, especially on protein and carb restricted diets.

This is true even if the diet is not calorically restricted. Which brings us to a rat study [2] discussed by CarbSane in her post “Ketogenic Diet increases Fat Mass and Fat:Total Body Mass Ratio”.

The study compared two diets, a control diet and a ketogenic diet:

The ketogenic diet had more than 6 times the fat of the control diet, the same amount of protein, and no carbohydrate at all. Since protein has to be converted to glucose on zero-carb diets, this ketogenic diet is actually protein restricted. The paper confirms that the ketogenic diet operated on the margin of severe protein deficiency:

[P]reliminary experiments using a KD with 20% protein (as used in children) caused undernutrition of the rats as shown by a significant loss of weight and hair (data not shown). For this reason we used 24% protein, equivalent to that used in controls. [2]

The ketogenic diet also had lower micronutrient levels (“Ash” and “Vitamin”) than the control diet, and much higher omega-6 levels.

Rats were fed ad libitum, meaning they could eat as much as they liked; they chose to eat twice as many calories on the ketogenic diet. This suggests that the diet was protein+carbohydrate deficient.

When protein+carbohydrate intake is deficient, muscle will tend to be catabolized for protein. This causes muscle loss. Meanwhile, the starvation response – especially when more calories are eaten – tends to lead to fat mass gain.

Muscle loss and fat mass gain are exactly what happened to these rats.
Rats on the control diet weighed more than rats on the ketogenic diet. But panel B shows that rats on the ketogenic diet had more white adipose tissue (WAT). The ketogenic diet rats had more fat mass but less body mass; they had obviously lost muscle and bone mass.

I believe this is due to eating too little protein and carbohydrate. Protein+carbs were 13% on the ketogenic diet, 75% on the control diet. 13% is just too little. For humans, we recommend a minimum protein+carb intake of 600 calories per day, which is about 30% of calories for a sedentary adult. Rats kept in shoebox cages are, of course, sedentary whether they would like to be or not.

I draw two conclusions:

1. If you’re deficient in protein+carb, you’ll lose muscle; and

2. Losing muscle may invoke the starvation response, causing you to gain fat.

Like the children on Johns Hopkins Hospital’s diet for epilepsy, these malnourished rats experienced stunted growth.
What is the alternative?

As we discussed in the first post in this series, Ketogenic Diets, I: Ways to Make a Diet Ketogenic, there are 3 ways to make a diet ketogenic. One of them is severe protein+carb restriction, but the other two – short-chain fat consumption and supplementation of the ketogenic amino acids lysine and leucine – can generate ketosis even if substantial carbs and protein are eaten.

So it’s worth exploring: with consumption of these ketogenic nutrients, plus substantial carbs and protein, can the health impairments of clinical ketogenic diets be avoided?

Via Nigel Kinbrum comes an interesting paper [3] exploring the use of branched-chain amino acids as an adjunct to ketogenic diets for epileptic children. Most branched-chain amino acids are ketogenic, so this is a good test of my hypothesis.

The study supplemented 45.5 g leucine, 30 g isoleucine, and 24.5 g valine to 17 epileptic children on the ketogenic diet. Leucine is ketogenic, valine glucogenic, isoleucine can be either. The results:

None of our patients had a remarkable reduction in the level of urine ketosis after the supplementation of branched chain amino acids. Moreover, no exacerbation of seizures in terms of frequency or intensity was noted in any of the 17 patients of the study.

Regarding the improvement of seizures, we found 3 patients who had already achieved a reduction of seizures on the ketogenic diet to experience a complete cessation of seizures, while 2 other patients had a further reduction of seizures from 70% on ketogenic diet to 90%. In 2 other patients, the percentage of improvement with the branched chain amino acids supplementation was even greater, achieving 50% and 60% before branched chain amino acids supplementation to 80% and 90% afterward.

There were no significant side effects; only a transient elevation of heart rate at the start of supplementation.

Importantly, supplementing these amino acids allowed more protein to be consumed for the same degree of ketosis:

The first observation we made was that by adding the branched chain amino acids, the fat-to-protein ratio of the diet changed from 4:1 to around 2.5:1 (depending on the patient’s weight) without causing any alteration in ketosis. [3]

Toxicity of Ketogenic Amino Acids

It may be possible to go higher than 45 g leucine per day. The authors acknowledge that they were being cautious in limiting branched-chain amino acid supplementation to that dose:

There is also the question of why we did not try to further increase the amount of branched chain amino acids supplementation because there were no side effects or a change in ketosis. As far as we know, it is the first time branched chain amino acids have been used in patients with epilepsy and we had to be very cautious with their administration. [3]

There is a risk of toxicity at high doses of leucine supplementation unless it is accompanied by the other branched-chain amino acids, isoleucine and valine:

Could we provide leucine alone as the most ketotic of branched chain amino acids? Providing exclusively leucine as an adjunctive treatment to ketogenic diet is impossible because it is toxic when consumed out of proportion to valine and isoleucine…. Lack of valine and isoleucine inhibits protein synthesis. The consequence is that leucine should not be consumed in large amounts without valine and isoleucine, even though only leucine promotes protein synthesis. [3]

Possibly this assessment is over-pessimistic: in rats leucine and isoleucine without valine had no significant toxicity at 5% of energy. [4] Leucine alone lacked toxicity in rat studies:

Recent studies in rats demonstrate no obvious toxicity, even with the administration of BCAA in doses that greatly exceed probable human intake. [5]

L-leucine, administered orally during organogenesis at doses up to 1000 mg/kg body weight, did not affect the outcome of pregnancy and did not cause fetotoxicity in rats. [6]

Lysine, the other purely ketogenic amino acid, is generally considered to have no significant toxicity. [7]
Considerations for the NBIA Kids

For the NBIA kids, Zach and Matthias, we want the diet to be as ketogenic as possible. This is important because glucose is unable to feed neurons due to the inability to make CoA in mitochondria and bring pyruvate into the citric acid cycle. If only ketones can feed the brain, it’s important to make as many of them as possible.

So we would like to give a lot of lysine and leucine. If we have to add other branched-chain amino acids to avoid leucine toxicity, it would be better to add isoleucine, which can be ketogenic, than valine which is only glucogenic.

The BCAA-for-epileptic-children paper [3] can help us judge safe dosages. Supplemental leucine can be at least 45 g/day, since that was give successfully to the epileptic kids. Lysine can be at least as much, since it is non-toxic. Already we’re up to around 400 calories from supplemental lysine and leucine, which is a healthy amount.

Is it necessary to give a lot of isoleucine and valine with leucine? That’s unclear. Leucine by itself may have special benefits for NBIA/PKAN kids.

Paper [5] shows an interesting set of reactions in the brain: leucine plus pyruvate can be transformed into alpha-ketoisocaproate plus alanine in brain mitochondria. This is extremely important, perhaps, because removing pyruvate from brain mitochondria might prevent iron accumulation in the brain.

Iron accumulation in PKAN is thought to result from pyruvate buildup in mitochondria. Pyruvate attracts cysteine, because pyruvate and cysteine are normally converted to downstream products with the aid of the PanK2 enzyme that is lost in PKAN. With the loss of PanK2, pyruvate and cysteine build up, and the cysteine chelates iron, trapping it in brain mitochondria.

If leucine can remove pyruvate from brain mitochondria, it may also diminish cysteine levels and therefore reduce iron trapping in mitochondria. The iron buildup that is so debilitating might be prevented or mitigated.
Conclusion

I believe the extreme limits on carb and protein intake in conventional clinical ketogenic diets are responsible for their growth stunting, muscle destroying, fattening effects.

In order to supply sufficient protein and carbs while maintaining ketosis, it is necessary to provide ketogenic short-chain fats and amino acids.

Clinical testing of such supplemented diets has so far produced encouraging results. Providing supplemental amino acids to epileptic children on ketogenic diets improved their health and allowed them to maintain ketosis with higher protein intake. Seizure frequency was reduced even as side effects diminished.

Personally, I wouldn’t attempt a long-term ketogenic diet without the aid of coconut oil (or MCTs), lysine, and the branched chain amino acids.

For the NBIA/PKAN kids, it seems that the amino acid supplements should be some mix of lysine, leucine, isoleucine, and valine, with the isoleucine and valine included solely to reduce leucine toxicity. The optimal amount of isoleucine and valine should be smaller than is found in branched-chain amino acid supplements, since leucine by itself may help prevent iron accumulation and increase ketosis. Also, one rat study [4] indicates that isoleucine alone, excluding valine, might be enough to relieve leucine toxicity. Excluding valine would increase the ketogenicity of the supplement mix.

I think the NBIA/PKAN kids will need to experiment with primarily lysine and leucine, and secondarily isoleucine and BCAA supplements, to see what mix works best for them.



Greetz[/I][/B]