DHEA enhances effects of weight training on muscle mass and strength in elderly women and men
DHEA Supplement Enhances Performance of Weight Lifting
Abstract
Plasma dehydroepiandrosterone (DHEA) levels and the form of dehydroepiandrosterone (DHEAS) decrease to 80 percent from 25 to 75 years. With ageing also, muscle mass and strength decrease. Published data on the effects on muscle mass and strength of DHEA replacement are inconsistent. The aim of this study was to determine if replacement of DHEA increases muscle mass and strength and/or increases the effects of heavy stress in women and men. During the last four months of the study of effects 10 ml DHEA replacement therapy, we performed a random, twice-blind, placebo controlled study using weight-lifting training (DHEA + exercise group, n= 29; placebo + exercise group, n = 27). The strength or thigh muscle volume of DHEA alone did not increase significantly at 6 months. However, the effect of 4 months of weight-lift workout on muscle strength was potentiated by DHEA therapy, measured by magnetic resonance pictures by one-repetition maximum measurement and cybex dynamometry, and by thigh muscle volume. In response to DHEA substitution, serum-like growth factor concentration increased. This study shows that DHEA replacement improves muscle mass and strength caused by strong resistance in elderly people and has the beneficial effect of improving muscle mass.
DHEAS and its form sulfated are present in people in much higher plasma concentrations than in other steroid hormones, which are considerably higher than in any other human steroid (22). Over 99 percent of plasma hormone is present as DHEAS, which is steroidally converted into DHEA (21). DHEA and DHEAS [DHEA(S)] are secreted in human and closely connected primate species by the zone reticularis of the adrenal cortex only. DHEA(S) adrenal production starts with puberty and peaks at age 20. Beginning at the age of 25, plasma DHEA(S) starts to decrease significantly and quickly, with the plasma DHEA(S) level at the age of 75 years down from 25 years to around 80%. The remarkable decline in DHEA(S) at age has led to a considerable concern about the possibility of the development, in addition to the development of aging-related disease processes, of DHEA(S) deficiency playing an important part in the deteriorated metabolic and physical functions.
A gradual decline in muscle mass and strength, which can lead to a fragility, is one of the changes that occurs when aging. There has been no definitive identification of the mechanisms responsible for this loss of muscle, which leads to sarcopenia. However, anabolic hormones, growth factors and physical activity are likely to decrease as one of the contributing factors. There are conflicting data on the effects that DHEA substitution has on muscle mass and strength. Morales et al. reported that in 8 men but not 10 women aged 50-60 years 6 mg of treatment with 100 mg DHEA per day increased muscular strength. Diamond et al. reported 10 per cent DHEA cream in skin for a daily 12 mo increase in the area of femoral muscle scans for 15 women between 60 and 70 years. However, Percheron et al. found in an extensive study involving 140 men and 150 women between the ages of 60 and 80 years that for a year 50 mg of DHEA daily had no effect on the thigh muscle area (MRI), or strength (MMRI). There has been no previous report of the interaction between DHEA replacement and high strength exercise. The replacement of DHEA causes minor increases in insulin-like growth factor I (IGF-I) and testosterone levels and the anti-glucocorticoid effect of DHEA has been reported. While these effects may not be enough to increase the muscle weight or strength in sedentary patients, the reaction to weight training seemed likely.
The objectives of this study were to determine if DHEA substitution for older men and women increases muscle weight and force and/or improves muscle mass and strength effects of a heavy-strength exercise.
STUDY DESIGN AND METHODS
The study was approved by the institutional review board of the Washington School of Medicine. Informed, written consent to participate in a study was provided to study participants.
In a study of DHEA replacement therapy plus resistance practice training, both men and women aged 65-78 years have been recruited from the community by direct mailing and mass media. There were 136 screenings of the volunteers. The test included a medical history, physical exams, blood chemistry analyzes, a urinalysis and a mammography analysis for men with prostate species antigen (PSA). Exclusion criteria include hormone-based therapy, hormone-based neoplasia history, ASP >2,6 ng/ml and active, serious diseases in the last year. Of the 136 volunteers examined, 33 have been excluded because they do not fulfill our criteria of eligibility. Another 39 opted not to take part. The remaining 64 volunteers have been allocated a randomly stratified randomized sex permuting process for receiving DHEA or placebo using a computer generated block. In addition, 56 of our randomized volunteers participated in our research on the effects on abdominal fat and insulin action of 6 mB of DHEA replacement. None of the people smoked. Those who took drugs were medicated for at least 6 ml for stable use. None of the volunteers regularly practiced, but all kept their body weight stable (±2 kg last year).
Study Design
In the last 4 m of the study, we carried out a randomized, double-blind, placebo-controlled studio of the effects of 10 mg DHEA alternatives therapy by adding weight-lifting training. DHEA or placebo were taken daily for 10 mos. participants For the last 4 mo of the course, all participants had weight training three times a week. The justification for starting weight training following 6 mo DHEA replacement was to allow the effects of DHEA per se to be distinguished from that of DHeA on the response to weight training instead of simultaneously with the dHEA therapy.
DHEA Replacement Therapy and Randomization
DHEA had been taken at bedtime at a dosage of 50 mg/day. We bought the DHEA and the Life Extension Foundation placebo capsules (Fort Lauderdale, FL). In the same appearance were placebo and active capsules. A member of the Division of Medicine Biostatistics of the Washington University School developed the randomization algorithm and a researcher who did not interact. The participants, the individuals who performed experiments, the person who dispensed the capsules and the evaluators of the results were blinded to the group assignment. Conformity was monitored at monthly intervals by the pill counts.
Weightlifting Program
A closely supervised weight training program was held for all participants. Three sessions each week were supposed to be completed and skipped, meaning that at least 48 sessions of weight training had to be conducted by each of the participants. The workouts were carried out by exercise technicians in our testing lab. The course consisted of nine exercises performed using the squat rack and Hoist machine (squats, leg presses, kne extension, knee bending, rows, straight line, seated chest presses, curl biceps and triceps) (Hoist Fitness Systems, San Diego, CA). The overall 1-RMs is calculated so the information required to change the strengths of the workout was provided, i.e. the amount of weight elevated during the workouts as the participants became more potent. Initially, two sets of each exercise were used to complete the weightlifting sessions, enabling six-eight repetitions of each exercise to be done by a total of 65% of 1-RM per exercise. After the 6-wk they have moved up to 3 sets of 8-12 replicates carried out with an initial 1-RM of 185 percent.
Assessments
The baseline strength, thigh-muscle volume, serum hormones and IGF-I were measured after 6 months and at the end of the study again.
MRI
Measuring the quantity of the thigh muscle, Proton MRI was used. The axial picture was obtained by a 1.5-T superconducting magnet (Siemans, Iselin, NJ) and by a T1 pulse sequence. Pictures have been purchased using 134 phase encoding steps for 256–256 images in a 16-bit format. Consistent location using coronal scout pictures to determine the starting point for an image acquisition (10 cm above the knee joint space). 8 axial images of 8 mm were obtained without a crossover gap. Both pictures were processed by the same blind professional technician using the image analysis programme (National Institutes of Health, Bethesda, MD). The total muscle volume from the eight axial pictures was calculated for the thigh (cm3). For repeat measurements of total volume of the thigh, the variation coefficient was <1,5%.
Muscle Strength Testing
1-RM testing.
The 1-RM test was done with the same Hoist training machines. The participants raised heavier weight more and more and recorded the maximum weight to be raised as 1-RM for each exercise (4). Participants were instructed first, shown how exercises can be carried out and then practiced before the baseline measurements during a trial session.
Isokinetic Dynamometer Testing
In a Cybex II isokinetic dynamometer (Lumex), the strength of knee extenders and flexor were also measured, with participants sitting at 120 degrees of flexion on their backs and hips, as described earlier (6). Testing at 0, 60 and 180 degrees per second was carried out. The arm of the dynamometer was attached to a flexion of 45° for the isometric test. Cybex testing has the benefit of minimizing the effects of neuromuscular learning on measuring results, as Cybex practice was not included in the training programme.
Diet
At baseline, at 6-months and at the end of the trial, the participants completed three-day food registers with a dietitian. Nutritionist IV records have been analyzed (First Databank, San Bruno, CA).
Blood Hormones and PSA
The serum DHEAS level was determined by the immunosorbent assay linked to the enzyme (Diagnostic Systems Laboratory, Webster, TX). Enzyme-linked immunosorbent assays were used to measure testosterone levels, sex hormone-binding globulin (SHBG) and IGF-binding protein-3 (IGFBP-3) levels; ultrasensitive radioimmunosurgeons were measured by estradiol levels (Diagnostic Systems Laboratory). In the main laboratory of the Diabetes Research Training Center, Washington University, the IGF-I was measured by radio immunoassay (9). The variation coefficients for these tests were <10%. A monoclonal antibody test determined the levels of PSA (Hybritech, San Diego, CA). These blood tests were done <40 hours after the last exercise after resistance training time.
Statistical Analyses
Base features of DHEA and control groups have been correlated for continuous variables with Student's t testing for unpaid samples and the categorical variables test for chi-square. Variance analysis of repeated measurements was used (ANOVA) for the comparison of time treatment effects with group factor (treatment) and factor of test (time). In repeated ANOVA tests, age and sex were entered as covariates. If an important treatment-by-time relationship was found, baseline variation to 6 mo, baseline changes to 10 mo, and changes from 6 mo to 10 mo were compared to baseline ANOVA and covariates of 6-month. In addition, paired t-tests were carried out to decide whether major improvements were made in the group. Analysis of the subjects who finished the study was conducted. Changes in muscle volume and strength were the key outcome tests. Changes in hormone, IGF-I and PSA concentrations were secondary outcome measures. We calculated that the shift in thigh muscle volume between groups, with a power of 0.9 and α of 0.05, would require a sample size of 20 ± 11 cm^3 per group. All statistical analyzes were carried out using SPSS version 12.0 (SPSS, Chicago, IL).
RESULTS
56 of the 64 people who participated in DHEA therapy and resistance training completed the 10-month report. Five participants in the placebo group fell (three were personal and two were not linked to the study for medical reasons) and three were dropped out from the DHEA group (1 for personal reasons and 2 for medical reasons unrelated to the study).
There were no major variations between randomized to placebo and resistance (PLB + EXER group) groups and DHEA plus resistance (DHEA + EXER group) groups in basic characteristics (Table 1). The serum DHEAS values in both groups have been on average 80% lower than the peak levels in our laboratory young people (alternatively 3,300 ng/ml), corresponding to a strong declin in DHEAS relative to age. During the 10-mm study duration (−0,9 ± 2,9 kg in PLB + EXER and −1,1 ± 4,2 kg in DHEA + EXER), body weight did not vary considerably.
| Placebo + Resistance Training (n = 27) | DHEA + Resistance Training (n = 29) | P Value | |
|---|---|---|---|
| Age, yr | 71±4 | 72±4 | 0.277 |
| Male/female | 13/14 | 15/14 | 0.688 |
| Ethnicity, %Caucasian | 93 | 91 | 0.606 |
| Weight, kg | 82.5±12.9 | 81.5±17.7 | 0.885 |
| Height, cm | 168.7±8.7 | 171.1±12.1 | 0.410 |
| BMI, kg/m2 | 29.0±4.4 | 27.9±4.5 | 0.351 |
| Serum DHEAS, ng/ml | 603.6±266.4 | 633.7±363.9 | 0.634 |
On average, 95 ± 9 percent at 6 mph and 93 ± 4 percent at 10 months of analysis were prescribed in the placebo category. DHEA compliance was 97±10% at 6 mio and 94±6% at 10 mio. The doses recommended were complied with. Given that all subjects required 48 training sessions, the exercise program was 100 percent compliant. The average attendance for the DHEA Group was 2.8 ± 0.3 workouts per week and the placebo group average was 2.7 ± 0.5 workouts/wk. The course was conducted for the DHEA group and for the placebo group for an average of 120 ± 10 days and 125 ± 19 days.
Diet
The energy consumption was measured with diet records without major modifications. The average energy consumption for the baseline of the DHEA + EXER Group was 2.99 ± 338 kcal/day and for PLB + EXER Group 2,276 ± 478 kcal/day for the DHEA + EXER Group at 10 m, respectively. The average energy input was 2.199 ± 338 kcal/day.
Muscle Thigh Volume
48 participants (23 PLB + EXER and 25 DHEA + EXER) have received MRIs. MRIs cannot be collected for a body metal, pacemakers, or claustrophobia in eight participants. In response to 6 months of DHEA therapy or placebo, there were no major changes in thigh muscle volume. In response to subsequent 4 mg resistance training in both DHEA and placebo-treated classes, substantial increases were observed in thigh muscle volume. In DHEA + EXER (7.6 ±7.3%) the rise in thigh muscle volume due to resistance exercise was considerably bigger than in PLB + EXER (3.1 ± 5.5%).
Muscle Strength, 1-RM
Data from 1-RM is inherently contradictory with three DHEA participants and two placebo participants due to arthritis pain, muscle strain and unexplained causes in two persons and had to be discarded. Another Placebo Community member did not carry out the 1-RM examination due to foot surgery. Table 2 shows the outcomes of the 1-RM evaluation with the rest of the 50 participants. During the first 6 mg of therapy with DHEA or placebo, no major differences were found in muscle strength measured by 1-RM. For the six drills, significant changes in 1-RM were replied to the 4 m weight training in both classes. The magnitudes of 1-RM increase in the DHEA group were still higher than in placebo, and statistically slightly higher gains for three exercises, leg pressures, chest pressure and knee extension in the DHEA group, compared to the placebo group (Table 2). Related responses were made for women and men.
| Placebo + Resistance Training (n = 24) |
DHEA + Resistance Training (n = 26) |
Treatment × Time P Value | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline | 6-mo | 10-mo | Baseline | 6-mo | 10-mo | ||||||
| Leg press, lb | 114±35 | 115±40 | 134±38† | 116±37 | 117±40 | 149±44*† | 0.008 | ||||
| Chest press, lb | 76±32 | 78±33 | 91±37† | 75±33 | 78±35 | 99±41*† | 0.022 | ||||
| Biceps curl, lb | 38±18 | 41±17 | 51±25† | 36±18 | 40±20 | 55±25† | 0.605 | ||||
| Seated row, lb | 86±28 | 89±28 | 115±37† | 89±30 | 94±34 | 124±41† | 0.463 | ||||
| Knee flexion, lb | 100±37 | 102±34 | 126±41† | 99±29 | 103±36 | 136±49† | 0.222 | ||||
| Knee extension, lb | 105±36 | 109±31 | 163±51† | 113±36 | 118±31 | 196±65*† | 0.027 | ||||
Muscle Strength, Cybex Dynamometry
For the first 6 months DHEA or placebo therapy, there were no major improvements in force measured by Cybex dynamometry. Both the DHEA and placebo participants made considerable gains during the following 4 months weight training. However, for all torque measures with the exception von isometric knee flexion, in the DHEA the rise in knee extension and knee flexion torque caused by training was considerably greater than in the placebo community (Table 3). Related improvements were made both women and men.
| Placebo + Resistance Training (n = 27) |
DHEA + Resistance Training (n = 29) |
Treatment × Time P Value | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline | 6-mo | 10-mo | Baseline | 6-mo | 10-mo | ||||||
| Knee extension | |||||||||||
| Isometric, ft-lb | 81±23 | 83±24 | 89±22‡ | 79±28 | 81±31 | 99±31*† | 0.008 | ||||
| 60°, ft-lb | 87±19 | 84±21 | 89±19 | 85±28 | 84±24 | 95±23*† | 0.024 | ||||
| 180°, ft-lb | 60±20 | 59±18 | 62±18‡ | 60±22 | 60±21 | 69±21*† | 0.012 | ||||
| Knee flexion | |||||||||||
| Isometric, ft-lb | 60±18 | 58±16 | 62±18 | 62±19 | 61±22 | 67±21‡ | 0.421 | ||||
| 60°, ft-lb | 60±19 | 60±20 | 64±18‡ | 58±15 | 59±17 | 69±20*† | 0.029 | ||||
| 180°, ft-lb | 43±19 | 47±19 | 49±18‡ | 47±17 | 47±18 | 58±19*† | 0.041 | ||||
Serum Hormone and IGF-I Levels
DHEA substitute therapy increased the levels of serum DHEAS to the average young range (Table 4). Serum testosterone dramatically improved (Tar3-times) in women to the young normal range, but it didn't improve significantly in males as a result of the DHEA replacement therapy. Serum estradiol in men increased by 30% and in women by 70% following DHEA treatment (Table 4). Substitution of DHEA has led to small but substantial rises of serum IGF-I. In reaction to DHEA substitution there have been no major improvements in the sex hormone-binding proteins or IGFBPs. For PLB+EXER group and 123±42, 116+±56and 119+±60nM for DHEA + EXER group and 6MB respectively (P=0.276), SHBG was 129 ±87, 130 ±83, and 132+±83nM for the DHEA+EXER group. In the PRED + EXER group and 4,444 ± 1.646, 4,371 ± 1.630, and 4,339 ± 1,727 ng/ml for baseline DHEA+ExER group, 6 months and 10 months, respectively (P = 0,517), IGFBP-3 was average at 4,008 ± 150, 41,464 ± 1,566, and 4,014 + 1,529 ng/ml respectively.
| Placebo + Resistance Training (n = 27) |
DHEA + Resistance Training (n = 29) |
Treatment × Time P Value | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline | 6-mo | 10-mo | Baseline | 6-mo | 10-mo | ||||||
| DHEAS, ng/ml | |||||||||||
| Men | 602±243 | 595±312 | 497±201 | 684±234 | 3,748±306*† | 3,218±346*† | |||||
| Women | 606±304 | 636±415 | 579±369 | 567±288 | 3,633±433*† | 3,401±469*† | <0.001 | ||||
| Testosterone, ng/ml | |||||||||||
| Men | 5.1±1.3 | 5.3±1.2 | 5.3±1.4 | 4.8±1.4 | 5.3±1.1 | 5.5±1.4 | |||||
| Women | 0.3±0.2 | 0.3±0.1 | 0.3±0.2 | 0.5±0.4 | 1.4±1.4*† | 1.5±1.9*† | 0.001 | ||||
| Estradiol, pg/ml | |||||||||||
| Men | 19.3±4.0 | 19.4±3.6 | 17.0±3.1 | 22.1±6.7 | 30.7±8.5*† | 29.1±7.5*† | |||||
| Women | 13.5±3.6 | 16.5±7.6 | 15.0±3.1 | 13.1±6.2 | 24.1±8.3*† | 22.3±7.3*† | <0.001 | ||||
| IGF-I, ng/ml | |||||||||||
| Men | 156±65 | 143±56 | 157±63 | 169±44 | 184±40*‡ | 193±40*‡ | |||||
| Women | 153±53 | 146±54 | 156±56 | 155±54 | 196±71*‡ | 202±51*‡ | 0.002 | ||||
Adverse Events
Over the duration of the review, there were no significant adverse effects. For men in the DHEA group and for 1.4 ± 0.8, 1.8 ± 1.1 and 1.7 ± 1.1 ng/ml, respectively, the PSA plasma amounts (basalin, 6 ml and 10 months) were 1.8 ± 1.1, 1.6 ± 1.2 and 1.5 ± 1.0 ng/ml.
DISCUSSION
Our findings indicate that DHEA substitution alone does not increase muscle weight or strength in men and women in elderly individuals substantially. This observation is consistent with the findings of Percheron et al's extensive analysis of DHEA substitution. Morales et al., on the other hand, registered an improvement in intensity in 8 men, but not 10 women, following DHEA. That may be that Morales et al. is using a dosage of DHEA of 100 mg/day, whereas Percheron et al. used a dose of 50 mg/day in this study.
The present research offers new evidence that the efficacy of high-resistance muscle hypertrophy and strength training in older men and women is substantially enhanced by DHEA replacement. This study was added to a study of the effect of DHEA surrogacy on glucose resistance and insulin action. It was intended in conjunction with height lifting exercise to provide preliminary evidence on the effects of DHEA replacement on musclar mass and strength. Finding an important potencial impact of DHEA on the growth of muscle mass and strength as a result of weight formation provides the basis for further studies designed explicitly to clarify the mechanisms by which DHEA replacement produces this reaction.
The discovery that DHEA substitution results in increasing the serum IGF-I concentration is a key indication of the potential mechanism (Table 4). While this rise has been minor, it can also increase DHEA substitution to skeletal IGF-I isoforms. It is especially striking to see that DHEA replacement could boost the increase in the muscle contracture-induced IGF-I isoform mechanical growth factor (MGF).
Testosterone has anabolic effect on the muscle tissue which strongly stimulates the benefits of a strong weight and strength resistence exercise. In this research, DHEA substitution led to a triple rise in the levels of testosterone in women. This discovery poses the likelihood that the growth of testosterone may have contributed to the impact of weight lifting on muscle mass and strength by substitution of DHEA. The possible arguments against this are the results that males who have not had a substantial rise in testosterone have had the same potential impact on DHEA substitution as females and that the actual testosterone level was still low in females with testosterone substitution, while improved.
Glucocorticoids influence skeletal muscles, and plasma cortisol levels and the elevated cortisol in the elderly in response to physiological stressors. The role of DHEA is anti-glucocorticoid. The improvement in muscle mass and strength training through substitution for DHEA seems to be regulated in part by counteracting the catabolic influence of cortisol rises caused by exercise tension.
Rodent research has shown that ageing contributes to chronic NF-μB activation and an increase in inflammatory cytokines production. Human levels are growing with advancing aging of IL-6, TNF-α, and C-reactive protein (CRP). The predictors of impairment are high levels of IL 6 and acute process protection including CRP, ICAM-1 and fibrinogen, which are mediated by inflammatory cytokines. Inflammatory cytokines influence skeletal muscles catabolically and are thought to play a role in sarcopenia growth. A steroid hormone part of the steroid receptor family (PPARα) is the peroxisome proliferator activated receptor-α (PPARα) activator. Activated PPARα reduces inflammation by adjusting NF-ŚB transcription activity adversely. The active protein-1 (AP-1) activator and the STAT paths both exercise anti-inflammatory effects. Thus, another process by which DHEA can potentiate the effect of muscle mass and strength resistance is a decrease in cytokine inflammatory activity.
Intra-abdominal fat and changes in the insulin action and glucose metabolism have previously been shown to reduce DHEA substitution. The present data show that substitution of DHEA often increases muscle mass and strength as a result of intense resistance in elderly men and women. DHEA has the added benefit.
