Not a creature was stirring … except for St. Nicholas…

Carnitine Prevents Frailty
And may reverse it

By Will Block

Are you afraid of aging? For most people—even those who are very healthy—there are many concerns that arise, especially when considering one’s family history and its genetic biases. As I grow older, the concern that bothers me the most is the potential onslaught of frailty. In my family there have been many who had a hard time getting around as aging started to set in.

Frailty is a biological syndrome of diminished energy reserve and loss of the ability to adapt to stress. In other words, there is a reduced resistance to stressors due to decline in multiple physiological systems. A stressor is a chemical or biological agent, environmental condition, external stimulus, or an event that causes stress to an organism.

Frailty Is Also a Geriatric Syndrome

Frailty is also a geriatric syndrome characterized by muscle weakness, sarcopenia, and fatigue, and is associated with several adverse health outcomes, including disability. To be frail is to be without energy, strength, and stamina.

For a busy man such as Santa Claus, frailty can be a career-ending condition (with all those gift bags to haul and many rooftops and chimneys to climb). As it can be for the rest of us who also keep a demanding pace.

The truth is that therapeutic interventions for geriatric frailty are challenging. Moreover, they are unquestionably complicated because of inadequate understanding of its biological foundations.

Aging Includes Functional Decline

Aging entails functional decline, loss of autonomy, and a wide spectrum of adverse outcomes as suggested in the scientific literature. Due to a planet-wide rise in life expectancy, the preservation of physical function and prevention of disability as we age are among our highest clinical and health priorities. Frailty is one of the main factors that adversely affects successful aging and leads to adverse health consequences—mainly falls and delirium—following what were previously of far smaller consequences.


The truth is that therapeutic
interventions for geriatric frailty are
challenging.


The Rate of Aging Depends on Muscle Carnitine Levels

Recent studies indicate that L-carnitine (hereafter carnitine) is important for energy production in skeletal muscles, and there is a negative correlation between advancing age and muscle carnitine levels. It is useful to note that acetyl L-carnitine does everything that regular carnitine does, plus it also can cross the blood/brain barrier and enhance cognitive functioning, while regular carnitine does not.

Carnitine deficiency contributes to geriatric frailty. Muscle carnitine levels decrease with advancing age in both humans and mice.1 This 27-year-old paper demonstrated that although blood carnitine levels did not appear to significantly change with age, carnitine levels in skeletal muscles from healthy individuals showed a strong age-related decline for both free and acetylcarnitine levels.


This is the first study of its kind that
was conducted to investigate the
effects of the carnitine supplement on
frailty status among
the frail or pre-frail elderly.


Minimize the Occurrence of Frailty in Geriatrics

Age-associated carnitine deficiency from a variety of causes—including organic cation transporter mutation and carnitine palmitoyltransferase II deficiency—may potentially explain the relationship between carnitine-associated mitochondrial dysfunction and geriatric frailty. Therapeutic agents that can prevent or reverse carnitine deficiency in older adults may minimize the occurrence of frailty in geriatric populations.


Amino acid deficiencies—including
deficiency of carnitine—have been
proposed to be associated with its
pathophysiology.


New Study Shows Anti-Frailty Benefits of Carnitine

Amino acid deficiencies—including deficiency of carnitine—have been proposed to be associated with its pathophysiology (a convergence of pathology with physiology). Nonetheless, the efficacy of carnitine supplementation on frailty status has not been documented. Thus, a new study aimed to determine the effect of carnitine supplementation (1.5 g/day) for 10-weeks on frailty status and its biomarkers and also physical function, cognition, and nutritional status among pre-frail older adults in Klang Valley, Malaysia.2

This study was a randomized, double-blind, placebo-controlled clinical trial conducted among 50 pre-frail subjects randomized into two groups (26 in the carnitine group and 24 in the placebo group). The subjects were honed down from more than 600 community dwelling individuals aged 60 years and above, with no known terminal and mental illnesses.

All subjects were instructed to take the supplementation as prescribed on the bottles (one capsule [500 mg], 3 times daily, for 10 weeks.


Frailty Index score and hand grip test
were significantly improved in
subjects supplemented with carnitine.


The Criteria and the Index

Outcome measures included frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile.

The Fried criteria are a popular approach to the assessment of geriatric frailty which encompass the assessment of five dimensions that are hypothesized to reflect systems whose impaired regulation underlies the syndrome. These five dimensions are:

• Unintentional weight loss

• Exhaustion

• Muscle weakness

• Slowness while walking

• Low levels of activity

The second tool was the Frailty Index (FI), an accumulation of 40 deficits, a short form of the original 70-item FI accumulation of deficits. Reportedly, this tool is reliable for frailty assessment in clinical research. It is recommended to be used in intervention studies involving frailty prevention and treatment.

Other physical function assessments included hand grip test, 30-second chair stand test, 8-ft time up and go test, 2-minute step test, gait speed test at rapid pace, peak expiratory flow rate test, and shoulder strength test. The results indicated that the mean scores of FI score and hand grip test were significantly improved in subjects supplemented with carnitine as compared to no change in the placebo group.

Based on Fried criteria, four subjects (three from the carnitine group and one from the control group) transited from pre-frail status to robust after the intervention.


Based on Fried criteria, four subjects
(three from the carnitine group and
one from the control group) transited
from pre-frail status to robust after
the intervention.


Three Races of Malaysians

In the study, both male and female subjects from three races composing the Malaysian community were included. This made the sample representative of the study population (pre-frail community-dwelling Malaysian older adults). Only six subjects dropped out, and two subjects were excluded from the final analysis.

First Study to Measure Carnitine Supplement on Frailty Status

This is the first study of its kind that was conducted to investigate the effects of the carnitine supplement on frailty status among the frail or pre-frail elderly. Once again, significant improvement in the carnitine group was only reported in the FI score and hand grip test.

Moreover, the percentage of mean changes scores were significantly different between the two groups in frailty status and hand grip test.


Improving frailty status as measured
by the hand grip test and exhaustion,
can be explained by
carnitine’s enhancement of
mitochondrial function.


Study Enhanced Mitochondrial Function

Carnitine has a significant effect in improving frailty status in general, and hand grip test and exhaustion in particular. These improvements can be explained by the effect of carnitine in enhancing mitochondrial function. This effect on mitochondrial function includes correcting the cellular energy supply deficit, through facilitating the transport of long chain fatty acids—the main source of energy in skeletal muscle—into the mitochondria; facilitating the removal of short and medium chain fatty acids that accumulate during metabolism; and maintaining the proteins and lipids in the optimum level.

Carnitine supplementation may increase the rate of fatty acid oxidation, preserve muscle glycogen, and increase the production of the adenosine triphosphate (ATP). These mechanisms improve the energetic metabolism in muscular skeletal tissue, and improved muscle function and reduced fatigue and exhaustion.

Other Carnitine Studies

The findings of this study regarding the effect of carnitine on frailty were compared with other studies that reported the effects of carnitine supplementation among older adults. However, it should be noted that the findings were different and varied depending on the subjects’ inclusion criteria and the targeted outcomes.


The intervention with 2 g/day of
carnitine for 6 months among
centenarians showed no significant
changes on free and total carnitine
blood levels.


Propionyl L-Carnitine for Aching Legs

Three months ago (in our September 2016 issue), we published an article showing that another form of carnitine, Propionyl L-Carnitine (PLC), could reduce intermittent claudication, a condition due to a walking-related, aching, cramping on-and-off pain caused by insufficient blood flow to the legs. In the study referenced in the article,3 PLC at 2 g/day taken for 4 months, enhanced walking time in a study that employed 239 patients between the ages of 40 and 75 years.

In the present study, the effect of carnitine on frailty status was assessed using the FI accumulation of deficit tool. The results showed that FI scores significantly improved. Previous studies did not use the FI tool to define frailty status changes with carnitine supplementation; therefore, the effect of carnitine on frailty was further discussed according to its effects on Fried criteria and other physical and functional status tests.

Hand Grip Test Significance

The effect of the intervention on hand grip test was significant, evidenced by differences in the percent of mean changes between the two intervention arms. Most people’s hand-grip strength gradually lessens as they age. Moreover, maintaining decent hand-grip strength levels can enable the elderly to more readily complete tasks of everyday living, and may even help them stay alive longer.

A 2007 study published in The American Journal of Medicine concluded that lower hand-grip strength readings are a reliable predictor of an increased mortality rate.4 Testing hand-grip strength can help to monitor this decline and can give an indication of risk. It is known that skeletal muscle is carnitine-dependent, as this muscle depends on fatty acid oxidation as the main source of energy.


A previous study that included 66
centenarian adults who received
carnitine supplementation showed
significant improvement in MMSE
due to the intervention.


Self-Report Feelings of Being More Energetic

Exhaustion criteria improved due to the carnitine intervention evidenced by the significant association found between the carnitine group and self-report feelings of being more energetic. This finding is consistent with other studies conducted on different groups of older adults which reported significant improvement in physical and mental fatigue with the carnitine supplementation in different intervention periods, different intervention doses, and different carnitine derivatives (as already indicated).

Carnitine is an important contributor to cellular energy metabolism. A study published in 2003,5 aimed to evaluate the effects of carnitine supplementation on body composition, lipid profile, and fatigue in elderly subjects with rapid muscle fatigue.

This was a placebo-controlled, randomized, double-blind, two-phase study. Eighty-four elderly subjects with onset of fatigue following slight physical activity were included. Prior to randomization, all patients entered a 2-week normalization phase where they were given an ad libitum (as desired) diet. Subjects were asked to record their daily food intake every 2 days.

Before the 30-day treatment phase, subjects were randomly assigned to two groups (matched for male/female ratio, age and body mass index). One group received carnitine 2 g twice daily (n = 42) and the other placebo (n = 42). Efficacy measures included changes in total fat mass, total muscle mass, serum triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein (apo)A1, and apoB levels. The Wessely and Powell scale was used to evaluate physical and mental fatigue. Subjects were assessed at the beginning and end of the study period.

At the end of the study, the carnitine-treated patients showed significant improvements in the following parameters: total fat mass, total muscle mass, total cholesterol, LDL-C, HDL-C triglycerides apoA1 and apoB.


Carnitine supplementation has the
potential to improve physical function
and reverse frailty, particularly for
those suffering from fatigue and
weakness with a convenient dose.


Physical and Mental Fatigue Decreased

Wessely and Powell scores decreased significantly by 40% (physical fatigue) and 45% (mental fatigue) in subjects taking carnitine, compared with 11% and 8%, respectively, in the placebo group.

Reduced Fat Mass; Improved Fatigue Levels

Administration of carnitine to healthy elderly subjects resulted in a reduction of total fat mass, an increase of total muscle mass, and favorably effected fatigue and serum lipids.

The results of the study revealed that the changes in free carnitine, total carnitines, and acyl carnitine blood level were not significant between the two groups. This means that the intervention with carnitine had no effect on the blood level of free, total, and acyl carnitine. Previous intervention studies of carnitine among the elderly were reviewed. The intervention with 2 g/day of carnitine for 6 months among centenarians showed no significant changes on free and total carnitine blood levels.


In toto, Carnitine supplementation
had a favorable effect on the
functional status and fatigue in pre-
frail older adults.


Carnitine Can Be Synthesized from other Amino Acids

The consistent findings may be because carnitine is a nonessential amino acid, which the body can synthesize from other amino acids in presence of other micronutrients. Other reasons are the differences of the rate of carnitine uptake from different tissues, and the variation of storage of carnitine among different tissues (hepatic, renal, cardiac, skeletal muscle, and brain).

The current study did not find any significant effect on cognitive function among the study subjects. However, a previous study that included 66 centenarian adults who received carnitine supplementation showed significant improvement in MMSE due to the intervention.6 Subjects’ characteristics in this study7 might play a role in these differences. For instance, the participants’ mean MMSE score was very low (16.5) and the subjects had cognitive impairment, whereas in this study, the mean MMSE score, which was very high, indicated a normal cognitive function. So, it is not enough to conclude that carnitine has no effect on cognitive function based on the findings of the current study.


Carnitine supplementation can
improve physical function and reverse
frailty, particularly for those suffering
from fatigue and weakness with a
convenient dose.


The Potential to Improve Physical Function and Reverse Frailty

In conclusion, carnitine supplementation can improve physical function and reverse frailty, particularly for those suffering from fatigue and weakness with a convenient dose.

This principal study of this article2 utilized a full 10-week supplementation, blood monitoring at baseline and posttreatment, and multiple assessments of various functions.

In toto, Carnitine supplementation had a favorable effect on the functional status and fatigue in pre-frail older adults. Since it is safe to use and the recommended dose is reasonable, you might want to try it to help prevent the slings and arrows of frailty.

References

  1. Costell M, O’Connor JE, Grisolía S. Age-dependent decrease of carnitine content in muscle of mice and humans. Biochem Biophys Res Commun. 1989 Jun30;161(3):1135-43.
  2. Badrasawi M, Shahar S, Zahara AM, Nor Fadilah R, Singh DKA. Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial. Clin Interv Aging. 17 November 2016;11:1675-86.
  3. Luo T, Li J, Li L, Yang B, Liu C, Zheng Q, Jin B, Chen Z, Li K, Zhang X, Zhang J. A study on the efficacy and safety assessment of propionyl-L-carnitine tablets in treatment of intermittent claudication. Thromb Res. 2013 Oct;132(4):427-32.
  4. Sasaki H, Kasagi F, Yamada M, Fujita S. Grip strength predicts cause-specific mortality in middle-aged and elderly persons. Am J Med. 2007 Apr;120(4):337-42.
  5. Pistone G, Marino A, Leotta C, Dell’Arte S, Finocchiaro G, Malaguarnera M. Levocarnitine administration in elderly subjects with rapid muscle fatigue: effect on body composition, lipid profile and fatigue. Drugs Aging. 2003;20(10):761-7.
  6. Malaguarnera M, Cammalleri L, Gargante MP, Vacante M, Colonna V, Motta M. L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr. 2007;86(6):1738–44.
  7. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–57.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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