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Amino Acids for Super Humans. Part III
Sulfur, More Than Just Rotten Eggs
notice! this are 100% uncorrected show notes not originally intended for publication
In this episode we are going to tackle:
- methionine (essential amino acid, EAA)
- cysteine (conditionally essential amino acid)
- n-acetyl cysteine (acetylated variety of cysteine, not found in food sources)
- taurine (non-essential amino acid)
methionine
α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2SCH3. This essential amino acid is classified as nonpolar.- along with cysteine, methionine is one of two sulfur-containing proteinogenic amino acids.
- its derivative S-adenosyl ethionine (SAM) serves as a methyl donor è DNA; less well known: biotin & ALA (=alpha lipoic not linoleic acid) synthesis
- cysteine,
- carnitine, creatine
- taurine, choline
- polyamines, catecholamines
- lecithin, phosphatidylcholine, and other phospholipids
methionine & heart disease: improper conversion of methionine can lead to atherosclerosis.
- improper conversion is attributed to commonly occurring genetic and acquired factors including deficiencies of folate and vitamin B12
- folic acid is itself not biologically active, tetrahydrofolate and other derivatives after its conversion to dihydrofolic acid in the liver are required for the homocysteine "recycling"
- another way to convert homocysteine back to cysteine (one step away from methionine) requires glycine betaine (NNN-trimethyl glycine = TMG)
- recent evidence suggests that this betaine-homocysteine methyltransferase (BHMT) is of greater importance in the methione cycle than methione synthase (previously thought to be the major mechanism for homocysteine recycling)
- studies show methionine restriction without energy restriction extends mouse lifespan (e.g. Miller. 2005)
- problem: just rodent data, mechanism of action probably involves UCP1 (mitochondrial uncoupling) in brown adipose tissue, of which adults have little to none; overall, underlying mechanisms poorly understood
- human application / implications? impractical and not advisable to follow a no methione diet, but these results + the possibility of “overtaxing” the methionine cycle clearly suggest that “more ain’t always better”
cysteine & cystine
Cysteine is found in most high-protein foods, including:- animal sources (high cysteine content): pork, sausage meat, chicken, turkey, duck, luncheon meat, eggs, milk, whey protein, ricotta, cottage cheese, yogurt
- plant sources (low cysteine content): red peppers, garlic, onions, broccoli, brussels sprouts, oats, granola, wheat germ, lentil
we have to distinguish cysteine vs. cystine
- cystine = two cysteine molecules linked by a weak disulfide bond
- cystine can be used to produce glutathione by macrophages and astrocytes
- but lymphocytes and neurons prefer cysteine and must rely on the glutathione that is produced by the macrophages and astrocytes, if unoxidized cysteine is not available
- as so often: what matters is the proper ratio of cysteine to cystine for both groups to get their preferred substrate for glutathione synthesis
- cysteine content of undenaturated whey is 7.6-fold higher than that of casein; denaturated whey is mostly cystine, though
- denaturation takes place if whey is blended at high speeds (mechanically) or heated above 118°F ~ 48°C
- common forms to produce whey isolates
- ion exchange - uses various amounts of heat and is thus potentially damaging
- microfiltration methods – depends on method, but generally less damaging
- CFM – cross flow microfiltration yields a high quality (8i.e. low carb, low fat isolate), but only if cold filtration is explicitly mentioned, you can be sure that the whey is chilled during the filtration process
- cold filtration – here you are sure about the temperature, but not about the pressure; often used to produce concentrates (higher carb & fat content)
- advice: look for CROSS FLOW MICROFILTRATION @ low pressure & low temperature for an “optimal” whey isolate
- note: concentrates may be superior in terms of cysteine / cystine ratio, because they are less processed than isolates
- also noteworthy: there is little cysteine in soy; in fact so little that it is even artificially added to “good” soy proteins
other especially valuable sources of cysteine are
- milk and
- egg-white
*guess why: nourish the organism in his state of maximal growth > what does this tell you about the value of these nutrients for a “physical culturist”?
why not take straight glutathione?
- contrary to marketing claims, standard oral supplements are not absorbed, i.e. the glutathione does not reach the blood stream [Dr. Rouse talked about that in one of the SHR epigenetic shows]
- purported alternative NAC = n-acetyl cysteine = amine protected version of cysteine that is rapidly hydrolyzed in the body to the amino acid cysteine and may thus serve as a readily available highly absorbable substrate for glutathione production
n-acetyl-cysteine - NAC
I will not discuss its use in kidney injury or acetaminophene, paracetamol, etc. poisoning and other acute treatment strategies such as liver failure etc.evidence pro supplementation
University of Kentucky: Ferreira. 2011 - N-acetylcysteine amide & N-acetylcysteine amide both ineffective; but NAC, used as control effective in in-vitro muscle fibers
- NAC increased total force-time integral (FTI; N·s·cm)
Victoria University of Technology, Melbourne: Medved. 2004 > lower rise in K+ [potassium] = less fatigue
- intravenous NAC: 125 mg.kg-1.h-1 for 15 min and then 25 mg.kg-1.h-1 for 20 min before and throughout exercise
- the rise in plasma K+ concentration at fatigue was attenuated by NAC (P < 0.05). The ratio of rise in K+ concentration to work and the percentage change in time to fatigue tended to be inversely related (r = -0.71; P < 0.07)
- time to fatigue during NAC trials was correlated with Vo2 peak (r = 0.78; P < 0.05), suggesting that NAC effects on performance may be dependent on training status
Victoria University of Technology, Melburne: Medved. 2004 > enhanced muscle cysteine and GSH availability
- NAC intravenously infused at 125 mg.kg(-1).h(-1) for 15 min and then at 25 mg.kg(-1).h(-1) for 20 min before and throughout exercise
- Muscle TGSH (P <0.05) declined and muscle GSH tended to decline (P=0.06) during exercise. Both were greater with NAC (P <0.05).
- related study (also from Victoria University) > McCenna. 2006
Baylor College of Medicine, Houston: Reid. 1994 > NAC inhibits muscle fatigue in humans.
- NAC 150 mg/kg or 5% dextrose <> 12g NAC for adult human being 160pounds < unrealistic due to side effects (diarrhea)
- tibialis anterior electrostimulation
- @10 hz: NAC increased force output by approximately 15%; evident after 3 min of repetitive contraction, persisted for whole 30 minutes
- @40 hz: NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue
- NAC @ 150 mg.kg(-1) vs. saline <> 12g NAC for adult human being 160pounds < unrealistic, see above
- NAC delayed fatigue (130% baseline) and inhibited glutathione oxidation
- NAC capsules (9 ± 2 or 18 ± 4 mg/kg) or solution (0, 35, 70, or 140 mg/kg).
- Intensity of GI reactions to 140 mg/kg NAC was significantly higher than placebo
- Plasma cysteine concentration increased with NAC dose from 9.3 ± 0.7 μM (placebo) to 65.3 ± 6.7 μM (140 mg/kg);
- however, there was no difference (p > .05) in plasma cysteine for 70 mg/kg vs. 140 mg/kg
- plasma thiols are maximized by oral administration of 70 mg/kg
evidence against supplementation for strength athletes, specifically
University of Florida: Childs. 2001 > Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise.
- eccentric arm muscle injury
- vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d
- LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group
- higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha [prostaglandin]
- Fiber bundles incubated in 0.1-10 mM NAC exhibited a dose-dependent decrease in relative stresses developed during 30-Hz contraction (P < 0.0001) with no change in maximal tetanic (200 Hz) stress.
- NAC (10 mM) also inhibited acute fatigue.
how bad is oxidation, anyway?
University of Kentucky: Chambers. 2009 > NAC treatment reduces stretch induced glucose uptake in muscle fibers
- N-acteyl cysteine (NAC), a non-specific antioxidant, ebselen, a glutathione mimetic, or combined SOD plus catalase (ROS-selective scavengers) all decrease stretch-stimulated glucose uptake (P < 0.05) mediated by reactive oxygen species and p38 MAP-kinase
- Univ. of Melbourne: Merryl. 2010 > muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK >> “NAC prevented contraction-stimulated glucose uptake”
- vs. University of Melbourne: Merryl. 2010 > N-Acetylcysteine infusion does not affect glucose disposal during prolonged moderate-intensity exercise in humans.
- beware: “neither NAC infusion nor exercise significantly affected muscle reduced or oxidised glutathione” < 80 min of cycle ergometry at 62 +/- 1% of peak oxygen consumption not exhaustive enough?
NAC, general health & more
...NAC for visceral fatloss
- suggested by Marc McDougal & other, cf. mind & muscle forum
- hypothesis: tnf-alpha, il-6 < reduce inflammation = get rid of visceral fat
- sounds logical, but studies are missing
- dosing scheme with anecdotal evidence for effectiveness: 2x 600mg NAC + 1g Vit-C
- why vitamin C?
- Vitamin C is supposed to prevent NAC degradation to S-Nitrosothiols > whole blood deoxygenation
- toxicity evidence for NAC from human studies missing (same is true for protective effect of vitamin C, though)
University of Ankara: Ozgur. 2010 > in combination with EGCG protective effect against free radical damage in the liver by mobile phone radiation (guinea pig study)
- 300 mg/kg NAC injected !
- similar results in other studies on EM-radiation
protection against lead / liver carcinoma, eg. University of Léon, Spain: San-Miquel. 2006
... other (some not sufficiently verified) benefits
- solves mucus (COPD, common cold)
- supposedly (insufficient evidence) protective against destructive effects of hyperglycemia on pancreatic beta cells
- useful for glutathione repletion in autism
- treatment of obsessive-compulsive disorder (experimental)
- […] everything where increased glutathione levels would play a role
usefulness of chronic supplementation(?)
- in view of Childs. 2001 NAC is best been taken on non-workout days
- usual dosages range from 400-1200mg
- @True Protein its 7$ a 100g; ca. 100 day supply = not too expensive
my personal recommendation: if you are on a budget, better spend the money for undenaturated whey protein with a high cysteine to cystine ratio; you won’t be getting enough cysteine for glutathione production without side-effects from NAC alone, anyway
common adverse effects to NAC
- skin rashes,
- gastrointestinal problems, vomiting
- headache, dizziness, blurred vision
Taurine
mg Taurine /kg | |
Beef | 430 |
Beef liver | 688 |
Beef lung | 956 |
Beef spleen | 874 |
Beef tongue | 1752 |
Cheese | 61 |
Milk (regular) | 8.3 |
Milk (homogenized) | 151 |
Whey | 660 |
Pork (loin) | 610 |
Chicken (breast meat) | 160 |
Chicken (dark) | 1690 |
Poultry | 3280 |
Poultry (liver) | 4878 |
Turkey (7% fat) | 2100 |
Clam | 5200 |
Cod | 314 |
Fish (mixed) | 1000 |
Herring | 1544 |
Mussel | 6550 |
Oyster | 700 |
Salmon | 1300 |
Salmon (juice from can) | 22132 |
Shrimp | 310 |
Tuna | 2000 |
Whitefish | 1500 |
Taurine (2-aminoethanesulfonate) is the most abundant amino acid in the body and can be obtained preformed in the diet or synthesized from cysteine in the body
taurine accounts for only 3% of the free amino acid pool in plasma, but
- 25% in liver
- 50% in kidney
- 53%, in muscle
- 19% in brain
dietary sources, see table (left); generally found mainly in meat and fish
taurine synthesis
synthesis occurs in various tissues via 2 different, cysteine dependent pathways
- cysteine dioxygenase (CDO) pathway – liver, adipose tissue (recent, Ueki. 2009 “the physiological function of taurine in adipocytes is not known”, but clearly anti-inflammatory, TNFα may decrease CDO expression)
- cysteamine (2-aminoethanethiol) dioxygenase (ADO) pathway – almost ubiquitous
metabolic function(s)
- essential for development of the central nervous and visual systems
- a major constituent of bile
- Watanabe. 2011: Lowering bile acid pool induces obesity and diabetes through reduced energy expenditure
- you will notice the effect on stool with higher doses of taurine è diarrhea
- an important organic osmolyte
- both taurine and its precursor hypotaurine can act as antioxidants
neurological functions
- important: taurine actually crosses the blood-brain barrier
- Taurine is one of the most abundant amino acids in the CNS and plays an integral role in physiological processes such as
- osmoregulation,
- neuroprotection and
- neuromodulation
- T activates GABA(A) and glycine receptors
- T inhibits NMDA and Ca(2+) channels
- T counters negative effects of glutamate (mediated via Ca2+ influx modulation, cf. Bulley. 2010)
- various neuroprotective effects
- against ethanol toxicity (Taranukhin. 2010)
- against morphine (Zhou. 2011)
- against anything associated with prolonged N-methyl Daspartate (NMDA) receptor activation, e.g. by glutamate (Wu. 2005)
taurine and cancer, antioxidant & radical formation
- decreased levels of taurine in breast cancer (taurine = involved in normal cell apoptosis, not enough taurine?) – (Agouza. 2011) >> CORRELATION not causation(!)
- inhibits H2O2 formation in adipose tissue exposed to insulin
- capable of inhibiting ROS generation, cf. eg. Schaffer. 2009
- mechanism of action: taurine plays its antioxidant role not by directly scavenging ROS but rather by
- inhibiting the generation of these and/or
- by interfering with their oxidant actions
- there is at least one exception, since taurine does have the capability of scavenging a particular compound, hypochlorous acid, an oxidant that activates the tyrosine kinase signalling cascade that leads to the formation of inflammatory mediators
- T is frequently depleted in diabetic state (Schaffer. 2009)
- additional taurine restores insulin secretion in protein malnurished rats (Batista. 2011)
- studies also indicate that taurine exerts hypoglycemic effects by enhancing insulin action
- taurine increases glycogen synthesis, glycolisis and glucose uptake in the liver and heart of adult rats
- pancreatic islets from mice having taurine, secreted more glucagon than those from control ones at low glucose concentrations
- Taurine administration improved insulin sensitivity and controlled hyperglycemia and hyperinsulinemia in fructose-fed rats as well as it restored the glucose metabolizing enzyme (Nandhini et al. 2005)
- taurine has shown to better ameliorate insulin sensitivity in type 2 diabetes when compared to N-acetylcystein in a study with humans
- taurine has the ability to suppress the progression of diabetic nephropathy (kidney health) through its antioxidant effects
- Taurine exerts effects in glucose homeostasis through two known mechanisms:
a) its effects upon β-cell insulin secretion
b) interfering with the insulin signaling pathway and post receptor events
- purported mechanism for beneficial effects: cholesterol regulation via bile salts + its demonstrated ability to reduce oxidative stress and inflammation
- twenty two healthy male japanese, aged 18-25, the effects of 6g/day taurine supplementation during 3 weeks versus placebo (Mizushima. 1996)
- diet specially designed to increase their cholesterol levels < design flaw
- group receiving the taurine supplementation suffered significantly smaller increases in these parameters [total & LDL]
- increases HDL to LDL ratio (not seen as that important in 1996, not reproduced in ovariectomized rats by Choi, 2009) in rat study (Choi. 2006)
- 5 weeks supplemental taurine in drinking water
- “plasma concentrations of total cholesterol, glucose and LDL-cholesterol were significantly reduced”
- additional reduction in triglycerides (reproduced by Choi, 2009)
- lower liver weight (indicative of less fat accumulation)
- important: similar beneficial effects in high vs. normal cholesterol diets (Park. 1998)
- counterevidence from epidemiological studies: higher taurine levels in serum (and sulfur compounds in general) = lower HDL-C
- what if the bodies of these persons deliberately produce taurine to benefit from its positive effect on HDL?
- again: epidemiology = pretty worthless without understanding the underlying mechanisms of action
- a study with rats showed that microvascular inflammatory injuries caused by hyperglycemia, became reverted after supplementation with taurine (Casey. 2007)
- dosage: 200mg/kg = 32mg/kg; approx. 2.5g taurine per day
- Taurine has demonstrated to lower homocystein plasma levels: an independent marker of cardiovascular risk // cf. NAC can raise homocysteine!
- Taurine supplementation reduces platelet aggregation in diabetes patients
- 3g/day of taurine for 7 weeks; significant decrease in TG (of 8 mg/dl) while the group that had placebo presented an increase of 3g/dl ; obese patients (Zhang. 2004)
- Taurine is considered to decrease blood pressure (BP) through a mechanism consisting of an interference on the angiotensin II signalling, which is in charge of causing vasoconstriction and the subsequent increase in blood pressure
- in a double blind placebo controlled trial, 19 borderline hypertensive patients were supplemented with 6 g of taurine a day, what resulted in a significant decrease of systolic and diastolic BP, while the placebo group suffered no changes in this parameter
- anti-hypertensive effect probably partly due to reduction of norepinephrine
- even acutely / after heart failure: taurine can help patients with congestive heart failure - improves contraction of the heart muscle
taurine obesity & weight loss
- significant weight loss in previously mentioned study by Zhang: 3g/day of taurine for 7 weeks; significant decrease in TG (of 8 mg/dl) while the group that had placebo presented an increase of 3g/dl ; obese patients (Zhang. 2004)
- 2010 data from c. elegans, every scientist’s darling [transparent, cheap, genome is known, not too complex, etc.], also shows: add taurine = prevent weight gain (Kim. 2010a)
- previous study showed reduction in stress and thus decreased symptoms of aging in the same model (Kim. 2010b)
- T triggers lipolysis & PKA [protein kinase A] in insulin treated adipocytes (Pina-Zentella. 2011); two mechanisms
- stimulating cAMP-dependent PKA catalytic activity and
- favoring PKA activation by cAMP as a consequence of lowering the H(2)O(2) pool
- very recent finding: keeps bile acid levels high and thus prevents weight gain and obesity (Wantanabe. 2011)
taurine and cell (muscle) structure / ergogenic potential / other
- “cell volumizer” – rather helps with transportation of nutrients, but more importantly minerals across the cell membrane
- control of ionic flux and effect on osmoregulation è influencing anabolic processes (proper hydration = anabolic)
- useful for “back pumps” on roids
- Taurine exerts this action by altering phospholilpid mehyltranferase activity, an enzyme which determines the phosphatidylethanolamine (PE) and phosphatidylcholine (PC) content of the membrane.
- taurine elevates the PE/PC ratio, what gives place to an alteration of cellular membrane fluidity and the improvement of its ability to resist toxic insults. (Yamaguchi. 2001)
- also relevant for roid users: taurine = hepato-protectant; found to be effective against various toxins, eg. carbon tetra-chloride, hydrazine, 1,4-naphthoquinone
- joint health: decreasing the degradation of hyaluronic acid
- taurine is an effective stimulator of GH and PRL secretion in rats, and that the mechanism of this action involves the opioid peptidergic system in the hypothalamus (Ikuyama. 1988)
- T increased exercise duration to exhaustion in rats, but decreased concentrations of threonine (-16%), serine (-15~-16%), and glycine (-6~-16%) in muscle (Ishikura. 2011)
- 3% oral taurine in drinking water supplementation may increase muscle performance and reduce muscle injury caused by exercise (Dawson. 2002)
- vs. beta-alanine = taurine depletion!
- beta-alanine rats had only insignificant plus in running performance + lost weight + had sdepleted methionine levels, higher CK, but lower LDH
- taurine group had sign. higher glutamine levels
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