What are phytates and how do they affect absorption of minerals?

You've heard that spinach has a lot of iron, right? But what you may not know is that spinach is a poor way to get iron because of its content of phytate.

Some of the iron in spinach is bound to phytate. Most of the iron you get is absorbed in the small intestine's duodenum. It comes into the mucosal cell as either a free ion or as heme. If iron is attached to phytates, however, its resistant to disassociation in the gut.

One way to help improve the absorption is by cooking the spinach to break down ligands attached to the iron. And by combining protein with your spinach, you can cause the stomach to release more hydrochloric acid, lowering the pH and helping free up some more iron.

When people have stomach problems that inhibit their ability to release hydrochloric acid (such as when people become older), it's known that a lot of iron is not absorbed at all. In these cases, it may be important to increase the amount of iron in the diet (specifically heme iron from animal foods since its easiest to absorb), even supplement with iron.

Biochem of starvation

Humans didn’t always have restaurants and grocery stores to visit on every corner. As part of human evolution, in fact, most of the time it’s likely our ancestors were starving quite often and got pretty good at it while foraging and hunting.

It took the agricultural revolution to really make a shift to food aplenty. But starvation hasn’t gone away by any stretch. It’s a daily reality for much of the underdeveloped world.
And, a bit closer to my reality, my own great grandmother often shared stories with me about how she’d go for weeks without meals as a little girl.

To be able to survive from meal to meal, we depend on a starve-feed cycle. It refers to the changes in metabolism that allows variable fuel and nitrogen consumption to meet variable metabolic and anabolic demand (1). In plain English, it is what gives humans capacity to eat food well beyond caloric requirements and store it as glycogen and triacylglycerol to utilize when needed (1).

This is what happens to someone biochemically as they enter starvation.

Early Starvation State (about two-five days after last meal)

About two days after a last meal with insulin low and glycagon on the rise, glycogen is depleted and muscle proteolysis is predominating (1). The protein catabolism would release of a mix of amino acids high in alanine and glutamine into the blood (1p246).

The alanine stimulates glycogen and is taken up from the liver where it's deaminated for conversion to urea and where pyruvate can be used for gluconeogenesis (1p246). Gluconeogenesis is also made from recycled lactate, pyruvate and from glycerol from fat tissue lipolysis (1p245). Blood glucose levels are successfully kept normal (1p246).

Prolonged Starvation State (one week or longer after last meal)

As starvation becomes prolonged, the body enters a metabolic shift. The shift is away from the glycogen-depleting and muscle-protein-breakdown fasting state (1). The body now intends to conserve vital body proteins to preserve vital functions such as antibodies fighting infection, enzymes catalyzing reactions and hemoglobin transporting oxygen (1).

For energy, the body begins using fat conveniently stored in adipose tissue during a time when more calories were consumed than expended (1). Thus, the blood’s level of fatty acids increases as those fatty acids become fuel (1). The heart, liver and muscle all oxidize them, but not the brain because fatty acids can’t cross the blood-brain barrier (1). The brain can use glycerol backbones, however, and these largely replace amino acids and glucose as its fuel (1).

TCA cycle intermediates for gluconeogenesis eventually become depleted and low levels of oxaloacetate coupled with rapid production of acetyl CoA from fatty acid catabolism create accumulation favoring ketone bodies (1). The ketone bodies are valuable as an energy source for sparing protein (1).

To survive in a starvation state generally depends on stored fat before starvation, although ketosis can cause significant physiological damage and even death (1). The ketosis is kept in check as long as possible by directing glutamine to kidneys, but acidosis increases as ketone production accelerates (1). Once fat stores are used up the body starts on essential protein leading to liver and muscle function loss that ultimately leads to death (1).

Reintroducing Food

As a starved person begins to eat again, there are metabolic interrelationships between the liver, muscle and fat tissue. Triaylglycerol is metabolized normally, but glucose metabolism must be slowly re-established (1). The reason is because the liver extracts glucose poorly and ends up staying in a gluconeogenec mode for awhile after feeding (1).

But the hepatic gluconeogenesis is not producing blood glucose (1). It's providing glucose 6-phosphate for glycogenesis (1). It's an indirect pathway for glycogen synthesis because glucose is catabolized in other tissues (muscle, fat) and then sent to the liver to be converted to the glycogen (1).

Finally, after a few hours, gluconeogenesis declines and glycolysis predominates (1). The liver glycogen then can be sustained again by direct synthesis from blood glucose (1).

Reference List

1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
2. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

Other:

Johnstone AM. Fasting - the ultimate diet? Obes Rev 2007;8:211-22.
Cahill GF, Jr. Fuel metabolism in starvation. Annu Rev Nutr 2006;26:1-22.

How does fat get absorbed and stored as fat?

Fat is absorbed in the intestine contained in chylomicrons and then secreted into lymphatics (1). The lymphatics drain the intestine, then lead to the thoracic duct and deliver the chylomicrons into the blood at a site of rapid blood flow (1). The rapidity is necessary to distribute the chylomicrons well preventing them from coalescing (1). Then lipoprotein lipase, which is attached to endothelial cell survaces in the lumen of capillaries, acts on the chylomicrones to liberate fatty acids via hydrolysis (1). The fatty acids are taken up by adipocytes and reesterified with glycerol 3-phosphate to form triacylglycerols and be stored as fat droplets (1).

Reference

1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.

Why insulin is key for intracellular protein synthesis

When you’ve just eaten some protein, insulin, glucagon, growth hormone and glucocorticoids increase because of the presence of elevated amino acid concentration (1p232). The insulin promotes the protein synthesis and the other hormones have an opposite effect (1p232). Growth hormone is anabolic like insulin, although counterregulatory (1p232). Insulin to glucagon ratio favoring insulin stimulates protein synthesis enzymes and vice versa (1p232). The insulin is needed for uptake of amino acids across the cell membrane and antagonizing activation of amino acid oxidation by some enzymes (1p206-207).

Protein synthesis is also sensitive to multiple influences including stability of mRNA, amount of rRNA, activity of ribosomes, and (most important from diet), the presence of essential and nonessential amino acids in appropriate concentration to charge the tRNA and hormone environment (1p232). When amino acids are not present or not present in sufficient quantity, amino acid oxidation increases (1p232).

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

After my high-protein shake

I just got done working out, sort of; I did manage to break a sweat. Then I made myself a high-protein shake and was sure to include a banana for carbs. Why do I do this again? Aren’t carbs a bad thing?

Well, it turns out that I need those carbs to stimulate insulin secretion to promote tissue cell uptake and use of the amino acids (1p206)(1). For this reason, it doesn’t make too much sense to take protein with some other kind of sweetener. The insulin affects movement of amino cid transporters to the membrane and their activity while also antagonizing activation of some enzymes that oxidize amino acids—very important if you’re trying to put on muscle (1p206-207)! You don’t want glucagon to dominate, leaving you with protein degradation (1p207). At least I don’t. Insulin stimulates protein synthesis and inhibits its degradation (1p207).

My shake’s protein content happens to be made up of contain whey and casein. That’s a good thing for me because whey is considered a “fast” protein that’s quickly digested, absorbed and oxidized to get that protein synthesis I want (1p207); the casein, a “slow” protein, prolongs amino acid concentration in the plasma at a low degree to keep protein synthesis up and protein degradation by around 30 percent (1p207). It’s unclear if older people are better off with the faster proteins and if younger people are better off with the slower proteins (1p207), but I’m 30 so I take both just in case. Plus, that casein keeps me feeling full longer (personal experience).
What’s also great about my protein shake is its amino acid profile. Leucine is important for promoting protein synthesis in my liver, muscles and skin because it accelerates phases of mRNA translation (1p207); plus, it’s involved in a signaling cascade to stimulate the mRNA translation (1p207). Leucine is great for me. And the whey apparently causes a rapid absorption of that leucine along with other branched-chain amino acids isoleucine and valine (2). The other amino acids will promote protein synthesis too along with cell volume through intracellular signaling, like leucine does (1p207).

Pretty much because I’ve just eaten (and just worked out), protein synthesis is dominating in my body (1p208) and the high-protein is speeding recovery of my muscles, specifically the whey more than the casein (3;4). About 20 percent of the amino acids going into the liver end up used for protein synthesis (most of what stays in the liver) and nitrogen-containing compounds (like creatine, glutathione, carnitine, carnosine, and choline) (1p198). The other amino acids end up in the plasma (1p198). Some of the amount will be used for purine and pyrimidine bases, which mainly make up DNA and RNA.

Because 40 percent of body protein is in muscle, a lot of activity occurs there (1p223). The muscle catabolizes aspartate, asparagines, glutamate and the branched-chain amino acids to a greater extent (1p223). My muscles are especially liking the content of branched-chain amino acids from the whey (2) that are circulating (1p218). Enzymes in my muscles as well as heart, kidneys, diaphragm, adipose and other organs like the liver transaminate them to be further oxidized into energy or for reamination (1p224).

Glutamine, for example, is generated in the muscle through several pathways (1p226). One such pathway includes transamination of branched-chain amino acids combined with alpha-ketoglutarate to form branched-chain alpha-keto acid and glutamate, then an enzyme combines glutamate with ammonia to form glutamine (1p226). Glutamine synthesis is relatively higher in skeletal muscle, lungs, brain and adipose tissues (1p226).

Creatine, which contains nitrogen from amino acids arginine and glycine with methyl groups donated from methionine, is also functioning in the skeletal muscle for energy (1p226). If not used it doesn’t stay there forever, but leaves the muscle as creatinine to the kidney and is excreted in urine (1p226). I can use the excretion, in fact, as a great indicator of my existing muscle and rate of degradation (1p226).

Along with creatinine, the urine will have nitrogen from urea, amino acids, ammonia and uric acid (1p238). Feces may have amino acids and ammonia too (1p238). A calculation that shows my nitrogen balance—how much protein I consume versus how much nitrogen comes out—can help me measure whether or not my protein intake is adequate and if the quality of my protein is good (1p237). After a high-protein meal the balance may be more likely to be on the side of delivering a positive result.

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Farnfield MM, Trenerry C, Carey KA, Cameron-Smith D. Plasma amino acid response after ingestion of different whey protein fractions. Int J Food Sci Nutr 2008;1-11.
3. Buckley JD, Thomson RL, Coates AM, Howe PR, Denichilo MO, Rowney MK. Supplementation with a whey protein hydrolysate enhances recovery of muscle force-generating capacity following eccentric exercise. J Sci Med Sport 2008.
4. Cribb PJ, Williams AD, Carey MF, Hayes A. The effect of whey isolate and resistance training on strength, body composition, and plasma glutamine. Int J Sport Nutr Exerc Metab 2006;16:494-509.

Should I starve or should I receive bodily injury?

Last week while attempting to meet a deadline at work I skipped lunch and soon enough began hearing my stomach growl. The “hunger hormone” ghrelin, I knew, had kicked in; it would react with the receptors of my hypothalamus to release certain neurotransmitters and my brain would tell me I wanted macronutrients (1p299). Carbs, fats, protein, anything would do. But I didn’t have anything to eat so I thought, “What happens if I starve?”

The answer is pretty straightforward. My body’s insulin would drop while glucagon would rise (1p246). Muscle and fat tissue would also become a bit resistant to insulin (1p246). Protein synthesis would drop (1p246). Glycogen from my liver would start becoming used up and muscles would release a mix of amino acids for gluconeogenesis (stimulating the glucagon) (1p246). The liver would keep my blood sugar level stable (1p246). If I didn’t eat for awhile, then my tissues would keep using fatty acids and glucose, but also start using ketones (from the fatty acid oxidation) for gluconeogenesis too (1p246). This is an important step to limit to conserve body protein, but does increase acidosis (1p246). The body has a way to deal with that too: more glutamine directed to the kidneys produces ammonia that combines with hydrogen ions to make urea for excretion (1p246). Acidosis is corrected and the kidney simply uses the carbon skeleton of glutamine to make glucose (1p246).

Summary of Starvation –

• Glucagon up, insulin down
• Reduced mRNA for translate of proteins
• Protein synthesis drops
• Increased starvation leads to decrease in secretion of glucocorticoids including cortisol
• Few days of fasting or starvation, glycogen is depleted and muscles undergo proteolysis for gluconeogenesis
• As fasting continues, tissues use fatty acids and glucose, but also ketones from fatty acids.
• Decrease in protein catabolism.

Now I value my hard-earned muscle because, frankly, I don’t have much left. The thought of losing some amino acids from my muscle was something I wasn’t too OK about. But the alternative would be to not get my work done on time. If that should happen, I’d be in a load of trouble. In fact, my boss might consider causing me bodily harm. Well, probably not. But it could happen. So I thought, “What would happen if I did end up injured?”


Apart from hurting pretty bad, stress from trauma like from a gun shot wound or burn would cause a bunch of problems. Mainly, it would send hormones in my body into a frenzy; glutocorticoids (primarily cortisol), catecholamines, cytokines, insulin and glucagon would all shoot up (1p246). Unlike starvation, the insulin presence would inhibit use of ketones for energy, thus, leaving me defenseless against muscle wasting (1p246). I’d lose more fast-twitch muscle than slow-twitch muscle (1p247). And yet, because tissues would be resistant to insulin, it would be useless in guarding against hyperglycemia caused partly by elevated cortisol (1p247). The cortisol, in fact, would be promoting the proteolysis (1p247). Cytokines would mediate proteolysis as well as hormonal response (1p247). The cytokines and glucocorticoids are thought to start synthesizing proteins including acute phase reactant and acute phase response proteins that cause fever, further hormonal changes and blood cell count changes (1p247). Other protein synthesis would decrease (1p247). To cope with possible loss of blood or to restore circulation depressed by shock, luckily, I’d have release of aldosterone and antidiuretic hormone to promote renal sodium and fluid reabsorption (1p247).

Summary of Stress –

• Glutocorticoids (primarily cortisol), catecholamines, cytokines, insulin and glucagon all up
• Tissues becomes resistant to insulin and hyperglycemia results
• Cytokines change substrate use
• Cortisol remains elevated causing proteolysis and hyperglycemia
• Cytokines and cortisol thought to increase synthesis of some proteins in liver to modulate body’s response; albumin and transferring to diminish stress
• Release of aldosterone causing sodium and fluid reabsorption and increasing blood volume (helps diminish fluid loss)
• Basal metabolic rate elevated
• Protein catabolism and lipolysis
• Lipolysis does not produce ketones for ketogenesis because of insulin presence and cannot defend against muscle catabolism
• Muscle wasting – white first, then red
• Protein turnover worsened by immune and acute phase responses (fever, etc.)
• Protein degradation exceeds starvation
  

All in all, I prefer starvation over stress. And, thus, I skipped lunch. Turned out to be a good plan: My very nice boss (who wouldn’t hurt a fly) gave me part of her lunch later on.

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

Raw or pasteurized

Raw milk and undenatured whey has been claimed to be better for you than their pasteurized and ultra-high-heat treated alternatives. Considering, however, that protein simply becomes denatured anyway in your gut (1), it would hardly make sense to care whether or not it was denatured.

But a French study in the latest J Nutr and other studies explain that when milk protein is exposed to ultra-high heat (but not pasteurization), digestibility and nutritional content due can be affected (2-4). The change occurs not specifically due to denaturation, but due to Maillard reactions (reaction between amino acids and sugars) from heat, production of unusual amino acids such as furosine, and reduced availability of essential amino acids (2-4). Pasteurization resulting in partial denaturation of milk and whey has also been shown to create a biological significance on the bioavailability of nutrients such as folic acid (5).

Still, I fear microbes, so suggest avoiding raw milk. Instead, try low-temp processed milk. Undenatured whey is good because it's filtrated, the cleaner the better for flavor.

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Lacroix M, Bon C, Bos C et al. Ultra high temperature treatment, but not pasteurization, affects the postprandial kinetics of milk proteins in humans. J Nutr 2008;138:2342-7.
3. Corzo N, Lopez-Fandino R, Delgado T, Ramos M, Olano A. Changes in furosine and proteins of UHT-treated milks stored at high ambient temperatures. Z Lebensm Unters Forsch 1994;198:302-6.
4. Mauron J. Influence of processing on protein quality. J Nutr Sci Vitaminol (Tokyo) 1990;36 Suppl 1:S57-S69.
5. Gregory JF, III. Denaturation of the folacin-binding protein in pasteurized milk products. J Nutr 1982;112:1329-38.

Deamination and transamination

Deamination examples

The amino acid threonine has its amino group removed by threonine dehydratase (1p209). This particular amino acid is commonly deaminated along with glutamate, histidine, serine and glycine (1p209). In the case of thronine, the reaction proceeds with loss of water, which is why the enzyme catalyzing the reaction is called a dehydratase instead of a deaminase (1p209). Vitamin B6 is important for this reaction to occur (1p209). The amino group is used by periportal hepatocytes to synthesize urea (1p209).

Transamination examples

The transfer of an amino groupf from one amino acid to an amino acid carbon skeleton or alpha-keto acid occurs to feed protein synthesis (1p209). The enzymes include tyrosine aminotransferase, branched-chain aminotransferases, alanine aminotransferase, and aspartate aminotransferase (1p209). The enzymes can often require vitamin B6 in a coenzyme form (1p209). The reactions are reversible and are often used to create non-essential amino acids from essential ones except lysine, histidiene and threonine (1p209).

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

When insulin becomes denatured

Protein denaturation is the unfolding of the secondary or tertiary structures (1). For example, heat can denature proteins in eggs by disrupting hydrogen bonds and non-polar hydrophobic interactions and as a result the egg proteins coagulate during cooking (1). Alcohol, like heat, can also disrupt hydrogen bonds, and acids, bases and heavy metal salts denature proteins by disrupting salt bridges (1).

What are biochemical consequences of denaturation of insulin?

In the body, protein denaturation can affect processes biochemically. Native insulin, for example, in the presence of increased, urea may be denatured because of changes in pH or, in the presence of a thiol catalyst, may be denatured due to isomerization (2). The insulin, thus, is unable to properly cause cells to take up glucose as it should (2).

Reference List
1. Ophardt CE. 2003. “Denaturation of Proteins.” Virtual Chembook. Available at: http://www.elmhurst.edu/~chm/vchembook/568denaturation.html
2. Jiang C, Jui-Yoa Chang. 2005. Unfolding and breakdown of insulin in the presence of endogenous thiols. FEBS Letters, 579;18. Available at: http://www.febsletters.org/article/S0014-5793(05)00720-9/abstract.
3. Chemistry and Biochemistry Department of Ohio University [Web page]. “Proteins.” Available at: http://dwb4.unl.edu/Chem/CHEM869K/CHEM869KLinks/main.chem.ohiou.edu/~wathen/chem302/protein.html

What happens in untreated type 1 diabetes?

Type 1 diabetes is characterized by autoimmune destruction of beta cells in the islets of Langerhans, which results in lack of insulin secretion (1). Glucose, then cannot be taken up by cells leading to hyperglycemia and osmotic diuresis (1). The low insulin will also stimulate hepatic glycogenolysis and gluconeogenesis to produce glucose released into blood leading into accentuated hyperglycemia (1).

What’s more is that gluconeogenesis becomes chronic depleting body proteins to break down into amino acids (1). Muscle,in effect, atrophes converting to glucose and lost through the diuresis (1). Weakness, fatigue and weight loss all occur (1).

Insulin inhibits degradation of protein and increases protein synthesis (2). Opposite to this, lack of insulin creates an environment favoring glucagon leaving degradation of protein unchecked and protein synthesis diminished (2). The degradation occurs by action of proteases—lysosomal or proteosomal—or via the calcium-activated proteolytic degradation pathway (2p234). The increased protein degradation increases nitrogen output resulting in a negative nitrogen balance (2p232).

One example of proteosomal degradation relies on activation of ubiquitin, steps of which are inhibited by insulin (2p208). Insulin also antagonizes activation of a few enzymes—such as the phosphorylation of phenylalanine hydroxylase—responsible for amino acid oxidation (2). The catabolism of amino acids involve transamination or damination (2p209). The amino groups are form alpha-ketobutyrate and ammonia, which must be removed in the urea cycle (2p209).

A mixture of amino acids that is high in alanine and glutamine would be released into the blood (2p246). Alanine, in particular, is a preferred substrate for gluconeogenesis and also stimulates secretion of glucagon, which stimulates gluconeogenesis (2p246).

Deamination/transamination of glycine, serine, cysteine, tryptophan and threonine leaves skeletons oxaloacetate and pyruvate ready for glucose production (2p212). Apart from those, phenylalanine and tyrosine could also be used for glucose when degraded to fumarate (2p212). Valine and methionine are gluconeogenic and isoleucine and threonine are partially glucogenic and partially ketogenic (2p212). Leucine and lycine would not contribute to gluconeogenesis since theyare ketogenic and catabolized to acetyl CoA (2p212).

Because muscle protein provides most of amino acids, particularly in stress situations, muscle cachexia occurs (2p242). The degradation of fast-twitch muscle would be more pronounced than that of the red slow-twitch (2p242). The protein degradation would not be unlike that of starvation with each gram of nitrogen equivalent to 30g of hydrated lean tissue (2p246).

Ketoacidosis is also a logical result. Just as in fasting and starvation, lack of insulin in type 1 diabetes disabling uptake of glucose in cells would lead tissues to use fatty acid oxidation for energy (apart from amino acids) (2p247). Fatty acid oxidation provides energy through production of acetyl CoA, a TCA cycle substrate (2p160). The acetyl CoA use can end up in the "overflow" pathway of ketone body formation (2p160). The ketones would be used as a source of fuel, but in excess can disturb acid-base balance causing acidosis (2p160;2p247).

Reference List
1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.
2. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

When do you need arginine?

Arginine is used for synthesis of protein, agmatine, polyamines and creatine [1]. Because kidneys synthesize arginine usually in sufficient amounts in the urea cycle(releasing 2-4g daily), it's normally not necessary to attain it from the diet [1p196;229].

At times, however, arginine can become conditionally essential [1p229]. Such times would include protein malnutrition, excessive ammonia production, excessive lysine intake, burns, infections, peritoneal dialysis, rapid growth, urea synthesis disorders, or in the inflammatory state of sepsis [2]. A deficiency could result in fatty liver, poor wound healing, hair loss, skin rash and constipation [2].

Arginine is changed into nitric oxide causing blood vessel relaxation [2], which can lower blood pressure. Thus, should not be used by a patient with low blood pressure [3]. If suffering of sickle cell disease, arginine can worsen symptoms [3].

One should exercise caution if supplementing with arginine because the amino acid is known to result in anaphylaxis in patients with certain allergies [3]. Those on anticoagulants should note that arginine can increase risk of bleeding [3]. It can increase potassium levels, especially in liver disease patients [3]. And the amino acid can increase blood sugar levels so may be contraindicated for patients who are trying to control blood sugar levels [3].

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Mayo Clinic. "Arginine (L-arginine): Background." Available at: http://www.mayoclinic.com/health/l-arginine/NS_patient-arginine.
3. Mayo Clinic. "Arginine (L-arginine): Safety." Available at: http://www.mayoclinic.com/health/l-arginine/NS_patient-arginine/DSECTION=safety.

How is urea regulated?

Urea cycle regulation is dependent on dietary factors and hormone concentrations (1). A feed-forward regulation exists in that available ammonia causes more urea to be created (1). This can also mean that higher protein can also act as a feed-forward regulation since it increases urea enzyme levels (1-2). Ammonia can come from diet, from deamination, or bacteria in the GI tract inducing formation of carbamoyl phosphate by mitochondrial carbamoyl phosphate synthetase (1).

Other regulation also exists. First, synthesis of n-acetyl glutamate, which is the allosteric activator of the carbamoyl phosphate synthetase (2). The activator is made in the liver and intestine when stimulated by available arginine (1-2). Second, arginase is inhibited by ornithine and lysine making it able to become rate limiting (1).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Lieberman M, Marks A, Smith CM, Marks DB. Marks’ basic medical chemistry, ed 3. Lippincott Williams & Wilkins, 2008.

“Goods” and “bads” of extra protein in sports

While Dietary Reference Intakes for protein are 0.8g protein per kg for adults, data suggest athletes may need more depending on their sport, particularly strength-training athletes (1). Research also indicates that even non-athletes who weight train may benefit from the added protein (2). Endurance exercise sports such as cycling and running increase protein turnover, including a lot more oxidation amino acids, so it is suggested that extra protein would also be wise (3;4).

However, many athletes often exceed intake required (5). While the positive balance may not affect competitiveness, excessiveness does not encourage further muscle growth or strength gain (5). It should also be noted that strength-training itself also encourages improved utilization of dietary protein possibly reducing need of added protein (5). When consumed with carbohydrate, net protein balance during and after endurance exercise is improved, but there is little evidence of actual improved performance due to the extra protein (3). There is also little evidence that the extra protein will stimulate muscle growth or strength (6).

Because daily requirements for protein are set by amount of protein lost, any extra protein should be added to make up for the loss and to maintain nitrogen balance (5). Protein intake that is excessive can lead to potential complications such as in the kidneys (if disease is onset) (7-10) and possible bone fracture if acidosis occurs (11).

Reference List

1. Phillips SM. Dietary protein for athletes: from requirements to metabolic advantage. Appl Physiol Nutr Metab 2006;31:647-54.
2. Evans WJ. Protein nutrition, exercise and aging. J Am Coll Nutr 2004;23:601S-9S.
3. Gibala MJ. Protein metabolism and endurance exercise. Sports Med 2007;37:337-40.
4. Tarnopolsky M. Protein requirements for endurance athletes. Nutrition 2004;20:662-8.
5. Phillips SM. Protein requirements and supplementation in strength sports. Nutrition 2004;20:689-95.
6. Dohm GL. Protein nutrition for the athlete. Clin Sports Med 1984;3:595-604.
7. Pecoits-Filho R. Dietary protein intake and kidney disease in Western diet. Contrib Nephrol 2007;155:102-12.
8. Manninen AH. High-protein diets are not hazardous for the healthy kidneys. Nephrol Dial Transplant 2005;20:657-8.
9. Friedman AN. High-protein diets: potential effects on the kidney in renal health and disease. Am J Kidney Dis 2004;44:950-62.
10. Donini LM, Pinto A, Cannella C. [High-protein diets and obesity]. Ann Ital Med Int 2004;19:36-42.
11. Mardon J, Habauzit V, Trzeciakiewicz A et al. Long-term intake of a high-protein diet with or without potassium citrate modulates acid-base metabolism, but not bone status, in male rats. J Nutr 2008;138:718-24.

Spoonful of any kind of sugar makes the protein go down after exercise

It's clear that carbohydrates with protein affects insulin, thereby inducing glycogen synthesis. However, I was left thinking, “But what kind of carbohydrate is best?” And I found a study that suited my curiosity. One published in 2007 in J Int Soc Sports Nutr showed that 40 subjects who weight trained taking 40g of whey protein were also given 120g of sucrose, honey or maltodextrin (1). After 30 minutes, the honey group showed greatest glucose concentration and best degree of blood glucose maintenance; however, there was really no significant difference and either can be used (1).

Reference List
1. Tipton KD, Elliott TA, Cree MG, Aarsland AA, Sanford AP, Wolfe RR. Stimulation of net muscle protein synthesis by whey protein ingestion before and after exercise. Am J Physiol Endocrinol Metab 2007;292:E71-E76.

Can arginine make you look like Arnold?

Arginine is a precursor for nitric oxide, which relaxes vascular smooth muscle leading to improved blood flow and, thus, the flow of nutrients to muscles (1;2). Oral arginine appears to also stimulate growth hormone release, especially when taken with exercise (3). Supplementation with arginine didn’t increase body mass significantly in a study in 2008; although, when taken with creatine, arginine did improve endurance and power of muscle (2).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Little JP, Forbes SC, Candow DG, Cornish SM, Chilibeck PD. Creatine, arginine alpha-ketoglutarate, amino acids, and medium-chain triglycerides and endurance and performance. Int J Sport Nutr Exerc Metab 2008;18:493-508.
3. Kanaley JA. Growth hormone, arginine and exercise. Curr Opin Clin Nutr Metab Care 2008;11:50-4.

Will glutamine give you big guns?

You might think so.

In theory, glutamine supplementation appears to make sense. Supplementation increases plasma glutamine in the plasma (1), which is thought to support the immune system (2;3) because the immune system uses glutamine for energy production (4). Plus, because exercise causes muscles to increase use of glutamine, stores are depleted (4). However, according to a 2001 study showed glutamine does not have any “significant effect on muscle performance, body composition or muscle protein degradation” (5).

Reference List
1. Maughan RJ. Nutritional ergogenic aids and exercise performance. Nutr Res Rev 1999;12:255-80.
2. Williams MH. Facts and fallacies of purported ergogenic amino acid supplements. Clin Sports Med 1999;18:633-49.
3. Nieman DC. Exercise and resistance to infection. Can J Physiol Pharmacol 1998;76:573-80.
4. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
5. Candow DG, Chilibeck PD, Burke DG, Davison KS, Smith-Palmer T. Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol 2001;86:142-9.

Trans fats increase diabetes risk more than saturated fats

Saturated fats including trans fat can lead to a increased risk of cardiovascular disease mainly by raising cholesterol and causing a poor LDL:HDL ratio (1). Trans fat is thought to be more atherogenic because it has also been found to lower HDL cholesterol in studies (1-3).

But what about diabetes risk?

In 2006 a review on the literature of trans fats versus saturated fats in insulin resistance noted that while high intake of saturated fats may promote insulin resistance, it is too early to determine if trans fats create increased risk(3). However, a 2008 rat study published in Asia Pac J Clin Nutr (2) showed that rats fed a diet higher in saturated fats had decreased peripheral insulin sensitivity, but that if trans fat was included the effect was greater.

Biochemically the reason for the effects on insulin sensitivity from dietary trans fat may have to do with its potential interference with cell membrane functions and decreasing insulin concentration (3-5). Ultimately both saturated and trans fats decrease insulin concentration, but trans fat more so (3-5). Interestingly, a review in Atheroscler Suppl pointed out that conjugated trans fat appears to be the “most dramatic” of all fatty acids in impairing insulin sensitivity (5).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Ghafoorunissa G. Role of trans fatty acids in health and challenges to their reduction in Indian foods. Asia Pac J Clin Nutr 2008;17 Suppl 1:212-5.
3. Odegaard AO, Pereira MA. Trans fatty acids, insulin resistance, and type 2 diabetes. Nutr Rev 2006;64:364-72.
4. Bhathena SJ. Relationship between fatty acids and the endocrine and neuroendocrine system. Nutr Neurosci 2006;9:1-10.
5. Riserus U. Trans fatty acids and insulin resistance. Atheroscler Suppl 2006;7:37-9.

Do eggs raise cholesterol?

The presence of ovomucin, a natural trypsin inhibitor in eggs, can help block some of egg cholesterol absorption and bile acid reabsorption through enterohepatic circulation (1). Despite ovomucin, however, there does appear to be enough dietary cholesterol in eggs absorbed that can potentially cause increased cholesterol levels (2;3).

Reference List
1. Nagaoka S, Masaoka M, Zhang Q, Hasegawa M, Watanabe K. Egg ovomucin attenuates hypercholesterolemia in rats and inhibits cholesterol absorption in Caco-2 cells. Lipids 2002;37:267-72.
2. Levy Y, Maor I, Presser D, Aviram M. Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. Ann Nutr Metab 1996;40:243-51.
3. Applebaum-Bowden D, Hazzard WR, Cain J, Cheung MC, Kushwaha RS, Albers JJ. Short-term egg yolk feeding in humans. Increase in apolipoprotein B and low density lipoprotein cholesterol. Atherosclerosis 1979;33:385-96.

Good and bad reasons to cook eggs

Raw egg white contains avidin. As dietary protein is digested, the presence of avidin can bind to biotin tightly preventing its absorption into the body (1). Because biotin is used as a prosthetic group in acetyl CoA carboxylase, a biotin deficiency can then inhibit the carboxylation reaction catalyzed by acetyl CoA carboxylase that converts malonyl CoA from acetyl CoA and CO2 (2). The conversion to malonyl CoA is ultimately the reaction by which carbons of a fatty acid are contributed to by acetyl CoA (2). Cooking destroys the avidin, which is a good thing.

But wait, an article in the latest Journal of Nutrition explains that Maillard reaction products (result of heating proteins and sugars) may alter amino acid availability and reduce digestibility of certain proteins (3). It would lead to believe that you'd want your protein raw or microfiltered versus fried or treated with ultra-high temperatures. Sure enough, you'll get more protein from a raw egg, plus enzymes and vitamins.

In the end, if you're going to eat eggs at all (see next post on cholesterol), it's probably best to cook the egg minimally and take a quality multi-vitamin and an enzymes supplement. That way you don't accidentally get salmonella.

Reference List

1. Brody T. Nutritional Biochemistry. San Diego: Academic Press, 1999.
2. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
3. Lacroix M, Bon C, Bos C et al. Ultra high temperature treatment, but not pasteurization, affects the postprandial kinetics of milk proteins in humans. J Nutr 2008;138:2342-7.

Lovastatin versus cholestyramine for familial hypercholesterolemia

Along with the recommendation of exercise and a healthy diet (including a bit of red wine daily), both lovastatin and cholestyramine can be used in the treatment of familial hypercholesterolemia (1;2).

While lovastatin works as a HMG CoA reductase inhibitor to reduce cholesterol synthesis in the liver, cholestyramine acts as a bile acid-binding resin that increases fecal removal of cholesterol (1p152;3-4).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Netdoctor.co.uk. Familial hypercholesterolemia. Available at: http://www.netdoctor.co.uk/diseases/facts/familialhypercholesterolaemia.htm.
3. Netdoctor.co.uk. Questran (colestyramine). Available at: http://www.netdoctor.co.uk/medicines/100002209.html.
4. Medicine.net. Lovastatin (oral). Available at: http://www.medicinenet.com/lovastatin-oral/article.htm.