Peak Muscle Fitness

Can l-carnitine and ALA offer an aging population the fountain of youth?

Editor’s Note: More interesting research on anti-aging supplementation.

DIETARY SUPPLEMENTS MAKE OLD RATS YOUTHFUL, MAY HELP REJUVENATE AGING HUMANS, ACCORDING TO UC BERKELEY STUDY

Berkeley – Two dietary supplements straight off the health food store shelf put the spark back into aging rats, and might do the same for aging baby boomers, according to a study at the University of California, Berkeley, and Children’s Hospital Oakland Research Institute.

A team of researchers led by Bruce N. Ames, professor of molecular and cell biology at UC Berkeley, fed older rats two chemicals normally found in the body’s cells and available as dietary supplements: acetyl-L-carnitine and an antioxidant, alpha-lipoic acid.

In three articles in the February 19 issue of Proceedings of the National Academy of Sciences, Ames and his colleagues report the surprising results. Not only did the older rats do better on memory tests, they had more pep, and the energy-producing organelles in their cells worked better.

“With the two supplements together, these old rats got up and did the Macarena,” said Ames, also a researcher at Children’s Hospital Oakland Research Institute (CHORI). “The brain looks better, they are full of energy – everything we looked at looks more like a young animal.”

“The animals seem to have much more vigor and are much more active than animals not on this diet, signaling massive improvement to these animals’ health and well-being,” said former UC Berkeley post-doctoral fellow Tory M. Hagen, now an assistant professor at the Linus Pauling Institute at Oregon State University, Corvallis. “And we also see a reversal in loss of memory. That is a dual-track improvement that is significant and unique. This is really starting to explode and move out of the realm of basic research into people.”

Based on the group’s earlier studies, the University of California patented use of the combination of the two supplements to rejuvenate cells. Ames, through the Bruce and Giovanna Ames Foundation, and Hagen founded a company in 1999 called Juvenon to license the patent from the university. Juvenon currently is engaged in human clinical trials of the combination.

One of the three PNAS articles probes the reasons behind this rejuvenation, concluding that the two chemicals “tune up” the energy-producing organelles that power all cells, the mitochondria. Both chemicals are normally used in mitochondria.

Ames calls mitochondria the “weak link in aging.” Evidence has been piling up, he said, that deterioration of mitochondria is an important cause of aging. A significant cause of this deterioration, he believes, is the accumulation of destructive free radicals – byproducts of normal metabolism – that disable enzymes and other chemicals.

The combination therapy targets mitochondria to get rid of destructive radicals and to boost the activity of a damaged enzyme, carnitine acetyltransferase, that plays a key role in burning fuel in mitochondria. The researchers hoped that the anti-oxidant alpha-lipoic acid would do the former, and that flooding the cell with acetyl-L-carnitine, one of two proteins that the enzyme acts on, would achieve the latter.

Experiments showed that this regimen worked. Associate researcher Jiankang Liu of CHORI, UC Berkeley postdoctoral fellow David W. Killilea and Ames demonstrated that the enzyme carnitine acetyltransferase is less active in old rats than in young rats, and that it binds less tightly to acetyl-L-carnitine in older rats.

Supplementation with acetyl-L-carnitine or a combination of acetyl-L-carnitine and alpha-lipoic acid restored the enzyme’s activity nearly to that found in young rats and substantially restored binding to acetyl-L-carnitine.

“The acetyl-L-carnitine is protecting the protein and the higher levels are enabling the protein to work, while alpha-lipoic acid knocks down oxygen radicals,” Ames said. “Each chemical solves a different problem – the two together are better than either one alone.”

Ames and Hagen have long had an interest in mitochondria as they relate to aging, and they were intrigued by a 1999 Italian study that showed acetyl-L-carnitine, when fed to old rats, improved mitochondrial activity.

The two thought this might be a way to reverse the effects of aging on mitochondria, and in various trials found it to work to some degree. Free radicals were still damaging the cell, however, so they decided to pair it with one of the few antioxidants that gets into mitochondria, alpha-lipoic acid. Lipoic acid is produced by mitochondria and boosts levels of other antioxidants.

In the second of the PNAS studies, Hagen, Ames and colleagues compared 2- to 4-month-old rats to 24- to 28-month-old rats, all fed acetyl-L-carnitine in their water and alpha-lipoic acid in their chow.

After as much as a month on the supplements, the old and lethargic rats became more peppy, Ames said.

“We significantly reversed the decline in overall activity typical of aged rats to what you see in a middle-aged to young adult rat 7 to 10 months of age,” Hagen said. “This is equivalent to making a 75- to 80-year-old person act middle-aged. We’ve only shown short-term effects, but the results give us the rationale for looking at these things long term.”

They found also that the combination of lipoic acid and acetyl-carnitine improved mitochondrial activity and thus cellular metabolism, and increased levels of various chemicals known to decline with age, including ascorbic acid, an antioxidant.

In a third study, Liu, Hagen, Ames and colleagues fed old rats a similar diet of the two supplements and looked at memory function as measured by the Morris water maze test and a peak procedure for assessing temporal or time-based memory developed by Seth Roberts, professor of psychology at UC Berkeley. They found that supplementation improved both spatial and temporal memory, and reduced the amount of oxidative damage to RNA in the brain’s hippocampus, an area important in memory. In electron microscope pictures of cells from the hippocampus, mitochondria showed less structural decay in old rats that had a supplemented diet.

“We did two different tests for cognitive activity in rats, and in both it made a big difference to feed them this mixture,” Ames said. “Memory degenerates with age, and this makes them better.”

The analysis of nucleic acid damage in the brain was performed with post-doctoral researcher Elizabeth Head and Carl W. Cotman, professor of neurobiology and behavior, at the Institute for Brain Aging and Dementia at UC Irvine. UC Berkeley psychology graduate student Afshin M. Gharib worked with Liu to conduct the peak performance tests.

“In aging, you’re oxidizing the proteins in mitochondria and they lose activity,” Ames explained. “If some of that lost activity is due to binding for substrate or coenzyme – like binding of acetyl-L-carnitine by carnitine acetyltransferase – and you can raise the level of those, then you can reverse some of the loss.

“We showed, in fact, that that is what’s happening with acetyl-L-carnitine. Aldehydes from lipid oxidation are glomming onto that protein, and that is what appears to cause the reduction in binding activity. But if you raise the level of acetyl-L-carnitine, now it works.”

Hagen added, “With aging, we see so many different things that are occurring to mitochondria that then lead to consequences in the cell. If you tune up mitochondria you may have a means of at least delaying the onset of a number of age-related problems that we encounter, or we can in some ways, hopefully, reverse what has already taken place.”

The work was supported by grants from the Ellison Foundation, the National Institute on Aging of the National Institutes of Health, the Wheeler Fund of the Dean of Biology at UC Berkeley, the Bruce and Giovanna Ames Foundation and the National Institute of Environmental Health
Sciences Center at UC Berkeley.
Low Carb Diets vs. Low Fat Diets – Which Is Best?

Editor’s Note: While this latest study will surely not end the discussion about the healthiness of low carb diets, it does show that being on a low carb diet for six months does not seem to pose any health risk. Also, in addition to their concerns about anyone suffering from diabetes or high blood pressure starting the diet without medical supervision, we have heard non clinical reports of people who suffer from gout having problems with the low carb diet. As with any diet, low carb or otherwise, it’s always best to review the diet with a qualified health professional.

LOW-CARB DIET MORE EFFECTIVE THAN LOW-FAT DIET, ACCORDING TO NEW STUDY

DURHAM, N.C. — People who followed a low-carbohydrate, high-protein diet lost more weight than people on a low-fat, low-cholesterol, low-calorie diet during a six-month comparison study at Duke University Medical Center. However, the researchers caution that people with medical conditions such as diabetes and high blood pressure should not start the diet without close medical supervision.

” This diet can be quite powerful,” said lead researcher Will Yancy, M.D., an assistant professor of medicine at Duke University Medical Center and a research associate at the Veterans Affairs Medical Center in Durham, N.C. “We found that the low-carb diet was more effective for weight loss,” Yancy added. “The weight loss surprised me, to be honest with you. We also found cholesterol levels seemed to improve more on a low-carb diet compared to a low-fat diet.”

The study is the first randomized, controlled trial of an Atkins-style diet approach, which includes vitamin and nutritional supplements. Along with losing an average of 26 pounds, dieters assigned to the low-carbohydrate plan lost more body fat, and lowered their triglyceride levels and raised their HDL, or good cholesterol, more than the low-fat dieters. The low-fat dieters lost an average of 14 pounds.

Though the low-fat diet group lowered their total cholesterol more than the low-carb dieters, the latter group nearly halved their triglycerides and their HDL jumped five points. The low-carbohydrate group reported more adverse physical effects, such as constipation and headaches, but fewer people dropped out of the low-carbohydrate diet than the low-fat diet.

The results appear in the May 18, 2004, issue of the Annals of Internal Medicine. The research was funded by an unrestricted grant from the Robert C. Atkins Foundation. The study authors have no financial interest in Atkins Nutritionals, Inc. The study builds on earlier results by the Duke University Medical Center researchers showing a low-carbohydrate diet can lead to weight loss — the first study of the low carbohydrate diet since 1980. Yancy and co-investigator Eric Westman, M.D., are currently testing whether a low-carbohydrate diet can help diabetics control their blood sugar levels.

Despite the considerable weight loss experienced by the low-carbohydrate dieters, Yancy does not recommend an Atkins-style plan for patients attempting to lose weight for the first time.

” Over six months the diet appears relatively safe, but we need to study the safety for longer durations,” Yancy said. He also cautioned that the diet could present certain health risks, such as elevations in LDL cholesterol levels, bone loss, or kidney stones. This and other recent studies of the low-carbohydrate diet have not demonstrated that these health risks occur over short durations, but they might occur in people on the diet for long-term. It is especially important that people on diuretic or diabetes medications be monitored by a doctor because the low-carbohydrate diet affects hydration and blood sugar levels, Yancy said.

The 120 study participants were randomly assigned to either the low-carbohydrate, high-protein diet or the low-fat, low-cholesterol, low-calorie diet. All were between 18 and 65 years old and in generally good health, with a body mass index (BMI) between 30 and 60, indicating obesity, and a total cholesterol level of more than 200 mg/dL. None had tried dieting or weight loss pills in the previous six months.

The low-carbohydrate group was permitted daily unlimited amounts of animal foods (meat, fowl, fish and shellfish); unlimited eggs; 4 oz. of hard cheese; two cups of salad vegetables such as lettuce, spinach or celery; and one cup of low-carbohydrate vegetables such as broccoli, cauliflower or squash. They also received daily nutritional supplements recommended by Atkins — a multivitamin, essential oils, a diet formulation and chromium picolinate.

There were no restrictions on total calories, but carbohydrates were kept below 20 grams per day at the start of the diet. The low-fat, low-cholesterol, low-calorie group followed a diet consisting of less than 30 percent of daily caloric intake from fat; less than 10 percent of calories from saturated fat; and less than 300 milligrams of cholesterol daily. They were also advised to cut back on calories. The recommended daily calorie level was 500 to 1,000 calories less than the participant’s maintenance diet — the calories needed to maintain current weight.

Study participants were encouraged to exercise 30 minutes at least three times per week, but no formal exercise program was provided. Both sets of dieters had group meetings at an outpatient research clinic regularly for six months.

Others members of the Duke research team were Maren Olsen, Ph.D.; John Guyton, M.D.; Ronna Bakst, R.D.; and Eric Westman, M.D., who was co-principal investigator for the study. The researchers maintained exclusive control of all data and analyses.

Source: Duke University Medical Center
Date Posted: 2004-05-18
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