So with great confidence and joy, we present the compounds that can enable you to do what no previous generation has achieved. The ability to control your metabolism, and experience a higher quality of life than you ever imagined.
The 5 Metabolic Modifiers
That Improve Cellular Energy Production
“Well, I just don’t have the energy I used to.” Doctors hear this complaint more than any other, and until recently, they had no response other than to say (and perhaps you’ve heard these words yourself) “You’re just getting older.” Or how about this one: “Learn to live with it.”
You see, after ruling out anemia, hypothyroid or a disease-related cause of fatigue, physicians had no solution. And because they themselves were most likely experiencing the same thing, they thought it was pretty much hopeless. All of that changed when scientists—including my research group — discovered nutritional factors that control the efficiency of the Krebs cycle.
The Krebs (or citric acid) cycle is the biochemical assembly line that generates energy within each cell. The energy “factories” where this takes place are called mitochondria (my-toe-KONdree- ah).
For more than two decades, Bruce Ames and his colleagues at the University of California, Berkeley, looked at the connection between fatigue and mitochondrial efficiency.
They began by comparing the activity levels of young rats vs. old rats. To no one’s surprise, they found that young rats were far more active. And here’s where the new paradigm of aging comes in. While others made these observations and said, “oh well, that’s just the way it is,” the Ames group looked for the reason for this decline. In the metabolic model, in other words, there are no assumptions. If aging is associated with increasing fatigue, we should be able to learn the cause. And find a cure.
Cells make energy through oxidation, biochemical combustion of the fuel you eat, and the oxygen you breathe. The Ames group theorized that over time, the by-products of oxidation might damage the mitochondria, resulting in lower energy production.
Think of a factory where the product being produced also causes the machinery to rust. At a certain point, the factory will grind to a halt, and that’s exactly what happens to mitochondria. As cellular energy declines, so does organ function. As organ function declines, so does your health. It used to be inevitable, but thanks to Ames and his crew, this critical facet of aging can now be reversed.
In a series of experiments, a team of scientists from five research organizations1 gave acetyl-L-carnitine and alpha lipoic acid—nutrients found in small amounts in red meat and milk— to older rats. Within seven weeks they saw dramatic improvements in mitochondria function and energy production. This not only led to increased activity levels, but as Dr. Ames stated, “With the two supplements together, these old rats got up and did the macarena. The brain looks better, they are full of energy—everything we looked at looks more like a young animal.”Ames’ last point is perhaps the most compelling. Restored energy is important, but to also achieve dramatic improvements in memory was an unexpected and exciting “side-effect.” In other words, increasing cellular energy production appears to improve everything.
NOTE: In April 2013, a study was published in Nature Medicine suggesting that carnitine supplementation could increase risk for atherosclerosis.4 As usual, surprising reports like this need to be viewed in the context of prior research. After looking at all of the facts, Natalie and I conclude that acetyl-L carnitine is safe and beneficial.
In fact, a new meta-analysis of the research on carnitine and heart health was published by researchers from Mayo Clinic. This was a large systematic review of controlled trials that enrolled over 3,600 participants; making it the largest, most powerful scientific review of carnitine’s cardiovascular benefits.
The Mayo Clinic study was conducted with people who had experienced a heart attack. In this group, carnitine supplementation was associated with a 27% reduction in all-cause mortality, a 65% reduction in ventricular arrhythmias, and a 40% reduction in chest pain symptoms.
These impressive benefits occurred via increased mitochondrial energy production and improved circulation. The authors describe carnitine as an inexpensive therapy with an “excellent safety profile.”
Suggested use: 500-1,000mg/day. A must for vegetarians and others who don’t eat red meat.
- Alpha Lipoic Acid (ALA)
Alpha lipoic acid is a vitamin-like compound produced within mitochondria, where it acts as a regulating coenzyme. A form of alpha lipoic acid is found in foods like brewer’s yeast, liver, kidney, spinach, broccoli and potatoes, but none of the food sources actually raise tissue levels of ALA. Thus, virtually all alpha lipoic acid available today is created in a laboratory.
ALA is a spectacular antioxidant. While some antioxidants like vitamin C work only in water, and others like vitamin E work only in fatty tissues, ALA is both water and fat-soluble, meaning that it can work throughout the body. What’s more, it can rejuvenate other antioxidants and potentiates the benefits of alpha-ketoglutaric acid (AKG).
And that’s just for starters. Alpha-lipoic acid enhances energy production by stimulating AMPK, and as you would guess, also improves glucose disposal, making it a remarkably effective nutrient for anyone with prediabetes, type 2 diabetes, or Metabolic Syndrome.
If that’s not enough reason to supplement with alpha-lipoic acid, it can also help you lose weight by telling the liver and muscles to burn fat. Where adipose cells were off-loading fat into adjacent muscle, causing damage and destruction? Alpha-lipoic acid prevents that. Research has also revealed ALA benefits in immunity, strength, endurance, and cardiovascular health.
“Lipoic acid supplementation improved body composition, glucose tolerance, and energy expenditure. Lipoic acid increased skeletal muscle mitochondrial biogenesis with increased phosphorylation of AMPK and messenger RNA expression of PGC-1alpha and glucose transporter-4.”
Wang Y, Li X, Guo Y, Chan L, Guan X. Alpha-Lipoic acid increases energy expenditure by enhancing AMPK-peroxisome proliferator-activated receptor-gamma coactivator- 1alpha signaling in the skeletal muscle of aged mice. Metabolism. 2010 Jul;59(7):967-76.
Translation: Alpha lipoic acid has been shown in animals and humans to be a potent and multi-faceted Metabolic Modifier.
NOTE: for alpha-lipoic acid aficionados: a more potent form of ALA is showing up in health food stores, called R+alpha lipoic acid or r-ALA. This appears to be nearly 100% bioactive, whereas standard ALA is about 60% bioactive. Since the r-ALA is more than double the cost of standard ALA, however, Natalie and I continue to use standard ALA. Importantly, more than 90% of the published human research on alpha-lipoic acid has used standard ALA. Now, when someone tries to sell your-ALA, claiming that it is the only bioactive form, you can make an informed choice.
Suggested use: 100mg to 500mg of alpha-lipoic acid per day best taken in divided doses. If using r-lipoic acid, you can use less.
- Alpha-Ketoglutaric Acid
Although it sounds like something from a chemist’s lab, alpha -Ketoglutaric acid (AKG) is an essential nutrient found in every cell of the human body. In fact, AKG is the rate-limiting step in the Krebs cycle, meaning that an insufficient level can dramatically reduce cellular energy production. The best news? You can eat it. Human clinical trials have documented improvements in exercise ability and recovery time with AKG supplementation.
“This study has shown that nutritional supplementation with α-keto acids in healthy, untrained subjects significantly improved exercise tolerance, training effects, and [post-exercise] recovery.”
Liu Y, Lange R, et al. Improved training tolerance by supplementation with α-Keto acids in untrained young adults: a randomized, double-blind, placebo-controlled trial. J Int Soc Sports Nutr. 2012 Aug 2;9(1):37. DOI: 10.1186/1550-2783-9-37.
Suggested use: Natalie recommends 200 to 500mg per day for general energy support, and to double that on strenuous exercise days.
Every “turn” of the Krebs cycle produces an energy molecule known as ATP (adenosine triphosphate). At the split second that three phosphate ions are released, they are fused together with adenosine and ribose. Viola ATP! Couch potatoes rarely lack ribose but anyone who is strenuously active usually needs more. Thus, providing a ready pool of ribose allows you to optimize ATP production.11 D-Ribose can also help during periods of intense stress.
Suggested use: I use 1 to 6g per day of D-Ribose with sports and fitness professionals. Natalie recommends up to 5g per day for her patients with heart disease.
- Medium Chain Triglycerides (a.k.a. MCTs)
Dietary fats and oils are made of triglycerides, structures that contain three fatty acids attached to one glycerol molecule. Tri-glyceride, get it? These form chains containing 4 to 26 carbon atoms, with hydrogen atoms attached to them. The reason for this mini lipid lesson is that fats are classified according to the number of carbon atoms they contain. You will hear about short chain triglycerides (fewer than 6 carbons), medium chain triglycerides (6 to 12 carbons) and long chain triglycerides (ranging from 12 to 26 carbons). The vast majority of the fats and oils you eat, whether from an animal or a plant, are long-chain triglycerides.
What is special about MCTs (derived from coconut and palm kernel oil) is that they are easier to digest, absorb rapidly into the bloodstream, and are used primarily to provide energy rather than adding to your waistline. In fact, studies show that consuming MCTs can help you lose weight. That happens because they increase fat burning and exercise tolerance.
Because of this energy factor, MCTs are used by lots of people. Physicians use purified MCTs to help nourish premature infants. If you were recovering from a serious injury or infection, you most likely would be given MCTs in the Intensive Care Unit. Athletes use MCTs to increase stamina, and this remarkable Metabolic Modifier is turning out to be a key feature in The Metabolic Makeover.
Suggested use: MCT oil is available in health food stores, and because of its neutral taste, can be added to a smoothie, shake, or mixed with your salad dressing. We include a tbsp. in our Kick Start Super-Shake.