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Recommendation Number 4:
Mitochondrial Energy Optimizer

DOSAGE: Take 4 capsules daily in divided doses early in the day, or all at once upon wakening

Protect your Proteins against Glycation, Suppress Pro-Inflammatory Cytokines while Optimizing Mitochondrial Function

Aging causes irreversible damage to the body's proteins. The underlying mechanism behind this damage is glycation.

A simple definition of glycation is the crosslinking of proteins and sugars to form non-functioning structures in the body.209 The process of glycation can be superficially seen as unsightly creased skin. Glycation is also an underlying cause of age-related calamities including the neurologic, vascular, and eye problems.210-219 Carnosine is a multifunctional dipeptide that interferes with the glycation process.220-223 When compared to the antiglycating drug aminoguanidine, carnosine has been shown to inhibit glycation earlier in the process.*

Carnosine levels are reduced with age. Muscle levels decline 63% from age 10 to age 70, which may account for the normal age-related decline in muscle mass and function.221 Since carnosine acts as a pH buffer, it can keep on protecting muscle cell membranes from oxidation under the acidic conditions of muscular exertion. Carnosine enables the heart muscle to contract more efficiently through enhancement of calcium response in heart myocytes.224 Long-lived cells such as nerve cells (neurons) and muscle cells (myocytes) contain high levels of carnosine. Muscle levels of carnosine correlate with the maximum life spans of animals. Carnosine attenuates the development of senile features.

Carnosine is one of the few compounds that increase the life span of human cells in culture. Human fibroblasts divide 40 to 45 times before they become senescent.

The presence of carnosine allows the cells to divide 8 to 10 times more before they stop dividing, increasing cell life span 20% or more.225-227

The daily dose of a concentrated nutrient formula called Mitochondrial Energy Optimizer provides 1000 mg of carnosine. This dose is needed to provide enough anti-glycating carnosine to your proteins before being depleted by the carnosinase enzyme that rapidly degrades dietary carnosine.

How Much Carnosine is in a Typical Diet?

Health conscious people often limit their intake of meat. One downside to avoiding meat, however, is that meat is the most abundant source of dietary carnosine.

A human study sought to determine carnosine concentrations in blood plasma after eating beef.146 Each 7.1-ounce serving of ground beef used in this study naturally contained 248 mg of carnosine.

In the study’s first phase, meat foods were removed from the diet for 48 hours. When fasting blood levels were measured, no carnosine was present. After the subjects ate 7.1 ounces of ground beef, carnosine was detected in the blood within 15 minutes and continued to increase for several hours. After 5.5 hours, there was again no carnosine in the blood. This study clearly showed that 248 mg of carnosine does not provide the body with all-day protection against glycation reactions.

The reason carnosine disappears so quickly from the blood is the presence of an enzyme (carnosinase) that naturally degrades carnosine in the body. This study on carnosine blood levels confirms what Life Extension published eight years ago when we advised members that at least 1000 mg a day of carnosine is needed to overwhelm the carnosinase enzyme and protect against toxic glycation reactions.147,148

Commercial supplement companies are still selling 50-mg carnosine capsules and claiming that this low dose is effective. Based on this human study showing that the body degrades 248 mg of carnosine within 5.5 hours, consumers who take these 50-mg carnosine capsules are obtaining virtually no benefit.

In addition to 1000 mg of carnosine, the Mitochondrial Energy Optimizer supplies benfotiamine… the fat-soluble form of vitamin B1. Benfotiamine provides additional protection against glycation reactions while guarding cells against the toxic effects chronic glucose exposure. Even people with normal glucose levels encounter damaging sugar reactions over a lifetime. Benfotiamine protects against glucose-induced cell damage via three different mechanisms.228-231*

Optimizing Mitochondrial Function

A serious event that cause the loss of cellular vitality is the depletion of mitochondrial energy function.149-151,154 Cells require healthy mitochondrial activity to perform life-sustaining metabolic processes. As mitochondrial function weakens in our cells, so does the vitality of organs such as the heart and brain, or in some cases, the entire body.152,153

While CoQ10 is necessary for youthful mitochondrial energy function, there are other essential nutrients involved in the mitochondria’s “respiratory chain.” In order for the mitochondria to create the energy needed to sustain cellular function, fatty acids (which serve as the mitochondria’s fuel) must be transported through the cell membrane and into the mitochondria155-157 The amino acid acetyl-l-carnitine boosts mitochondrial energy production by facilitating fatty acid transport and oxidation within the cell.158-160

As the mitochondria burn fatty acids to produce cellular energy, it generates a host of free radicals in the process. That is why a mitochondrial antioxidant like lipoic acid is so critical. The Mitochondrial Energy Optimizer™ provides the more potent form of lipoic acid (called R-lipoic acid), along with a more effective forms of L-carnitine.

Mitochondrial Energy Optimizer™ incorporates the tremendous advances in our knowledge about the importance of maintaining mitochondrial integrity as we age. Scientists now know that mitochondrial decay in aging is a major driving force behind the aging process.149,152

Fatty acids that serve as the fuel for the mitochondria are pulled across the mitochondrial membrane by carnitines.155-157 As we age, we lose the ability to pull fatty acids across the membrane because of free radical damage that occurs inside the mitochondria.161 We call this leakage the “loss of respiratory control.” Mitochondrial Energy Optimizer™ helps restore mitochondrial respiratory control by lowering natural antioxidant leakage and boosting cellular levels of R-lipoic acid, acetyl-l-carnitine, and endogenous antioxidant enzymes.*

The Brain Regeneration Form of Carnitine

Brain cells communicate with each other because they are connected to one another by neurites (dendrites and axons). Neurites are long filament-like terminal branches of nerve cells that grow much like branches of a tree. Neurites function to provide the communication circuitry pathways between the nerve cells.

As we age, there is a loss of neurites, which results in slowed thinking as neural-connection pathways are reduced from many in number to only a few. The effect of the age-related neurite loss is that thought processing pathways, thinking time, and reaction times are all significantly diminished.

Acetyl-l-carnitine arginate is a patented form of carnitine that stimulates the growth of neurites in the brain.* Studies show that acetyl-l-carnitine arginate stimulates the growth of new neurites by an astounding 19.5% (similar to that of Nerve Growth Factor itself). Acetyl-l-carnitine arginate acts together with acetyl-l-carnitine to increase neurite outgrowth in rat pheochromocytoma PC12 cells.178

Acetyl-l-carnitine by itself stimulates neurite growth after five days by 5.6%. Acetyl-l-carnitine arginate, on the other hand, stimulates neurite outgrowth in the same time period by 19.5%…an increase of over three-fold!178 An equally impressive finding was the average length of the neurites produced by the acetyl-l-carnitine arginate is 21% longer than in the acetyl-l-carnitine-only group..178

When scientists compared the effects of acetyl-l-carnitine and arginine, the mixture gave the same growth results as acetyl-l-carnitine by itself, i.e. 5.6%. This study showed that acetyl-l-carntine arginate induced 3.48 times more neurite growth compared to acetyl-l-carnitine mixed with arginine.178

Additional Neurological Effects of Acetyl-L-Carnitine

The acetylated form of L-carnitine (acetyl-l-carnitine) facilitates the release and synthesis of acetylcholine by donating its acetyl group to the production of acetylcholine, an important neurotransmitter.179 Acetyl-l-carnitine also enhances the release of dopamine from neurons and helps it bind to dopamine receptors.180,181 Numerous human and animal studies validate the multiple beneficial mechanisms that acetyl-l-carnitine exerts in the brain.

Acetyl-l-carnitine is more effective than L-carnitine in carrying fatty acids across the membrane into the cell where they are burned as energy. Since 1995, Life Extension members have been supplementing with acetyl-l-carnitine and deriving the many benefits this form of carnitine has shown in published scientific studies. Acetyl-l-carnitine and acetyl-l-carnitine arginate work particularly well together because of the high amount of free carnitine contained in the acetyl-l-carnitine. With the discovery of acetyl-l-carnitine arginate, the benefits of acetyl-l-carnitine can now be greatly augmented. Mitochondrial Energy Optimizer™ provides both acetyl-l-carnitine and acetyl-l-carnitine arginate.

Suppressing Mitochondria-Generated Free Radicals

Free radical damage is a well established culprit behind premature aging.162 To counteract toxic free radicals, health conscious people supplement with antioxidants such as green tea, grape-seed, lycopene, gamma tocopherol, and other plant extracts.

Alpha lipoic acid is a particularly potent antioxidant because of its ability to boost glutathione levels inside cells to protect against mitochondrial-generated free radicals.182-188 Lipoic acid functions as a fat and water-soluble antioxidant.189 It easily crosses cell membranes to confer antioxidant protection to interior and exterior cellular structures.189,190

Alpha lipoic acid contains 50% “R”-lipoic and 50% “S”-lipoic acids. Most people don’t know that the active part of alpha lipoic acid is the “R”-lipoic acid isomer.189 R-lipoic acid is found in very small amounts in the tissues and is tightly bound to mitochondrial complexes. Due to the difficulty of isolating R-lipoic, researchers originally conducted studies using only alpha lipoic acid.

While the body can utilize both forms of lipoic acid, the R-lipoic form is far more biologically active. For example, the “R”-form improves ATP synthesis in isolated cells, whereas the “S”-lipoic form does not. The R-lipoic acid form was shown to increase cell membrane fluidity and transport.191,192

As the biologically active form of “alpha lipoic acid,” R-lipoic acid is directly involved in cellular metabolism. It is a vital component of the intracellular antioxidant cycle, able to scavenge a variety of free radicals and reactive oxygen species while recycling vitamins C, E and glutathione.192-197

R-lipoic acid readily crosses the blood brain barrier and has been shown effective for elevating intracellular glutathione levels.198 This biologically active lipoic acid isomer helps regulate neuronal calcium homeostasis,199 neuroprotective against excitotoxic insults199, regulates pro-inflammatory cytokines,201-204 and alters the expression of ‘toxic genes205* R-lipoic acid has been used to protect against adverse glucose reactions in the body and is recommended as a ‘neuroprotective agent.198,200,206-208 Because R-lipoic is the naturally occurring form found in mitochondrial complexes, it offers substantially greater benefits at significantly lower doses than the synthetic forms of lipoic acid currently available.

Mitochondrial Energy Optimizer™ contains this more potent R-lipoic acid, which provides more protection against free radicals than higher amounts of alpha lipoic acid.

Suppressing Inflammatory Cytokines

Normal aging is accompanies by an increase in pro-inflammatory cytokines that often cause a low level of chronic, systemic inflammation. Nutrients that suppress pro-inflammatory cytokines are thought to confer longevity benefits.

Interleukin-6 (IL-6) is an example of a pro-inflammatory cytokine that often increases with aging and is associated with many undesirable effects. A recent study of people who have reached or passed their 100th birthday reveals that they uniformly express lower than normal IL-6 levels.236

Luteolin is a flavonoid that is found in olive oil, green pepper, and perilla plant, and has been shown to lower pro-inflammatory cytokine expression in vitro and in vivo.237-239 In particular, luteolin is a strong IL-6 inhibitor that may work via several different mechanisms to reduce this lethal inflammatory cytokine. Some studies show that luteolin down regulates pro-inflammatory TNF-alpha activity to lower IL-6 levels. Other studies demonstrate that luteolin reduces NF-kappa B levels that control IL-6 production.240 Additional studies show that luteolin reduces across the board the majority of the most dangerous inflammatory factors in the body including NF-kappa Beta, TNF-alpha, IL-4, IL-5, and IL-6.240-243*

The upregulation of inflammatory genes is one of the cruelest aspects of the aging process. Luteolin is an ideal supplement that is orally very effective as a potent inhibitor of IL-6 and related inflammatory cytokines at low doses. Mitochondrial Energy Optimizer™ provides a potent luteolin concentrate in each daily dose.

Improving Systemic Energy Levels

Rhodiola is an herb that has been shown to support mental well being, improve associative thinking, increase short-term memory, calculation, ability of concentration, and speed of audio-visual perception in several human double blind crossover studies.232-234*

Rhodiolia works primarily on the mitochondria in the central and parasympathetic nervous system. In small doses, rhodolia increases the bioelectric activity of the brain and stimulates norepinephrine, dopamine, and serotonin, all major neurotransmitters.235*

Every study with Rhodiola that shows positive effects uses the Russian Rhodiola standardized to 3% rosavins and 1% salidrosides. The Russian Rhodiola became so scarce because of demand, that many manufacturers began using the wrong species of Rhodiola or the wrong concentrations of active principals. Life Extension uses only the original Russian formulation that demonstrated the greatest efficacy in published reports.235

Added Protection Against Free Radicals

The antioxidants produced naturally by your body such as superoxide dismutase (SOD) and catalase offer thousands of times more protection against certain dangerous free radicals than dietary antioxidants. Unfortunately, your body’s youthful supply of natural antioxidant enzymes such as SOD rapidly decreases as you get older.

The Mitochondrial Energy Optimizer™ includes a patented SOD catalyst to help replenish your body’s supply of SOD and enhance your natural antioxidant defenses against free radical assault. Three types of sprout concentrates—soy, corn and wheat—are included in this proprietary SODzyme™ blend to stimulate the endogenous production of antioxidant enzymes such as SOD that increase energy output in mitochondria.

SODzyme™ does not generally cause problems for those who are allergic to soy, corn or wheat, because it contains only the sprouts and not the mature plant that contains the greatest concentration of allergens. In human trials, SODzyme™ enzymes have been shown to increase serum and blood levels of SOD. The effects of increased SOD levels are to block inflammatory processes and provide relief from associated problems. Nonetheless, Mitochondrial Energy Optimizer is available with of without SODzyme™ for those who are hyper-sensitive to soy, corn or wheat.

A Comprehensive Anti-Aging Supplement

Mitochondrial Energy Optimizer provides nutrients that have demonstrated significant biological benefits at the cellular level. A look at the complete Mitochondrial Energy Optimizer formula reveals the comprehensive value of this energy-restoring mitochondrial supplement in only four capsules per day:

Carnosine	1000 mg
Acetyl-l-carnitine arginate DiHCl	750 mg
Acetyl-l-carnitine HCl	750 mg
R-lipoic acid	150 mg
Benfotiamine	150 mg
Vitamin B1	50 mg
Rhodiola rosea	150 mg
Luteolin	8 mg
SODzyme™ (sprout concentrates)	300 mg
(also available without SODzyme™)

The cost of taking all of the individual ingredients found in Mitochondrial Energy Optimizer™ would be prohibitive for most people. Life Extension members, however, gain access to these avant-garde nutrients at huge savings.

A bottle containing 120 capsules of the Mitochondrial Energy Optimizer™ retails for $82.00. If a member buys four bottles, the price is reduced to $54.75 per bottle. Mitochondrial Energy Optimizer also comes in a version without SODzyme™, at the same price. For more information see the Mitochondrial Section of this directory.

Note: It is important to take four capsules per day of the Mitochondrial Energy Optimizer with SODzyme™ in order to benefit from carnosine. The reason for this is because the body automatically metabolizes lower amounts of carnosine into an inert substance, but the body cannot quickly neutralize the amount of carnosine (1000 mg) contained in four capsules of Mitochondrial Energy Optimizer with SODzyme™. formula.

Caution: Individuals with anxiety, manic or bipolar disorder should not use Rhodiola. Those allergic to soy, corn, or wheat should take Mitochondrial Energy Optimizer without SODzyme™.

More Info on Mitochondrial Function

Top Ten Nutritional Supplements

1: Multivitamins and Minerals
(Life Extension Mix™)

2: Omega-3 Fatty Acids (Fish Oil)

3: Coenzyme Q10 (CoQ10)

4: Mitochondrial Function (MEO)

5: Hormone Balance (DHEA)

6: Brain Cell Function (Cognitex)

7: Bone Health (for women and men)

7a: Prostate Health (for men only)

8: Neural and Hepatic Health (SAMe)

9: Cardiovascular Health (Aspirin)

10: Vitamin K, Gamma Tocopherol (Super Booster Softgels)

References

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164. Harman D. Free radical theory of aging: a consequences of mitochondrial aging. Age 1983 6:86-94.

165. Miquel J, Fleming JE. A two step hypothesis on the mechanisms of in vitro cell aging: cell differentiation followed by intrinsic mitochondrial mutagenesis. Exp. Gerontol. 1984 19: 31-6.

166. Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 1994 91:10771-8.

167. Hagen TM., Yowe DL, Bartholomew JC., et al. Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase. Proc Natl Acad Sci USA 1997 94:3064-9.

168. Beckman KB., Ames BN., Mitochondrial aging: open questions. Ann NY Acad. Sci. 1998; 854:118-27.

169. Kerner J, Hoppel C. Fatty acid import into mitochondria. Biochim Biophys Acta. 2000 Jun 26;1486(1):1-17.

170. Turcotte LP. Role of fats in exercise. Types and quality. Clin Sports Med. 1999 Jul;18(3):485-98.

171. Jeukendrup AE, Saris WH, Wagenmakers AJ. Fat metabolism during exercise: a review. Part I: fatty acid mobilization and muscle metabolism. Int J Sports Med. 1998 May;19(4):231-44.

172. Aureli T, Miccheli A, Ricciolini R, et al. Aging brain: effect of acetyl-L-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy. Brain Res. 1990 Aug 27;526(1):108-12.

173. Ebeling P, Tuominen JA, Arenas J, et al. The association of acetyl-L-carnitine with glucose and lipid metabolism in human muscle in vivo: the effect of hyperinsulinemia. Metabolism. 1997 Dec;46(12):1454-7.

174. Paradies G, Ruggiero FM, Petrosillo G, et al. Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-Lcarnitine. Mech Ageing Dev. 1995 Oct 13;84(2):103-12.

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