Key Takeaways:
~ Muscle strength is approximately half genetically determined and half due to lifestyle and exercise.
~ Strength training increases muscle mass through myokines produced by muscle contraction and repair of microtrauma from maximal effort.
~ Genetic variants play a role in how much muscle mass improves with training, the response to myokines, and recovery time.
The goal of this article is to explain how resistance or strength training increases muscle mass, why it’s important for everyone’s health, and how to maximize the efficiency of muscle gain.
Members will see their genotype report below and the solutions in the Lifehacks section. Consider joining today.How Genes Influence Muscle Growth
Resistance training involves contracting muscles against weight to increase strength, power, endurance, and more. This type of strength training covers what people think of as weight lifting as well as body weight exercises, such as pushups, and resistance band workouts.
The heritability of strength measurements is around 50-60%.[ref] So while anyone can increase their muscle mass by lifting weights, there’s a fairly wide range in the amount of muscle that people gain. Not everyone will end up looking like Arnold Schwarzenegger or The Rock; genetics play a big role in how much muscle someone can easily gain without using performance-enhancing drugs.
Genome-wide association studies show that gains from training are influenced by multiple genetic variants — a polygenic trait. Moreover, people with similar genotypes respond similarly to exercise training.[ref] The research on genetic variants for athletic or strength training is extensive, but many of the studies show inconsistent results.[ref] Included in this article are genes that have both high-quality human studies and animal studies showing the mechanism of action.
Understanding your genetic propensity to gain muscle (or not) can help you prioritize the right supplements and training routine.
Context: Why is muscle important for everyone’s health – especially as we age?
Skeletal muscle plays an essential role in everyone’s metabolic health by absorbing glucose and regulating blood sugar levels. Loss of muscle mass contributes to metabolic disease.[ref]
Muscle power is essential in healthy aging – whether you are overweight or not.
A recent study of more than 2,500 people over the age of 65 looked at the importance of muscle strength in mortality risk. The study divided the people into four groups: lean + powerful, overweight + powerful, lean + weak, and overweight + weak.
The results showed that even with a BMI over 30 (overweight or obese), those with strong muscles had a significantly lower risk of all-cause mortality. The lean + weak and overweight + weak groups were both at a higher all-cause mortality risk.[ref]
Let’s dig into the science of how to build muscle and then look at how genetic variants for each component affect the gains from weightlifting. But first, a little background science on the composition of muscle tissue.
Background science on muscle tissue:
Genes play a big role in muscle fiber composition, with studies showing that it is about 45% heritable. There’s a lot of variability among individuals when it comes to muscle types.[ref] Of course, you likely knew this just from looking at the different body types in a crowd.
For example, type I muscle fibers, also known as slow twitch, don’t fatigue as quickly and are therefore helpful in aerobic or endurance training – think of the long, lean marathon runner. Type IIA muscle fibers, on the other hand, are better suited for medium-duration anaerobic exercise. Type IIA (fast oxidative) or type IIX (fast glycolytic) muscle fibers are best used for power and strength training.[ref] The ACTN3 gene encodes α-actinin-3 protein, which is almost exclusively restricted to type IIX muscle fibers, which are responsible for producing explosive, powerful contractions.[ref] A genetic variant that causes ACTN3 deficiency is associated with being less likely to be an elite power athlete and more likely to excel at endurance sports instead. (See your ACTN3 genotype in the Genotype Report section below.)
Satellite cells are special muscle-resident stem cells that are essential for muscle growth and repair.
Skeletal muscle cells are unique in that they can contain hundreds of nuclei, called myonuclei. They regulate muscle activity during exercise, and additional myonuclei are needed for sustained functional growth.[ref]
Below is a diagram of skeletal muscles.
Stressing Muscles for Growth and Strength:
There are two primary ways that muscles become stronger:[ref]
- Repeated muscle contraction
- Healing from microtrauma
Contracting muscles is an important trigger for muscle growth. Repeated contraction leads to muscle fiber hypertrophy by triggering the pathways that lead to protein synthesis. Myokines are inflammatory signals (cytokines) that are released by muscles during contraction (eccentric or concentric). They signal to the rest of the body, through receptors.
Lifting weights at your maximum limit causes a small amount of damage to the skeletal muscle. This micro-trauma triggers inflammation, which signals for repair and growth through muscle stem cells. Muscle mass is added by the growth of new muscle tissue in response to the micro-trauma. Satellite cells (muscle stem cells) are activated by the myokines released during maximal weight lifting.
Satellite cells are a type of muscle stem cell, found in the extracellular matrix of the muscle tissue. When satellite cells are activated, they can divide and migrate to the site of muscle damage. These muscle stem cells can then form either new myotubes or even whole new muscle fibers.[ref] Changes to satellite cells cause the decrease in strength and muscle mass in aging.[ref]
When looking at how muscle mass and strength increase from resistance training, we need to consider:
- Myokines – inflammatory signals for growth
- Muscle tissue protein synthesis, signaling
- Innervation and vascularization
Myokines: Inflammatory signals released with muscle contraction
Myokines are released by muscles when they contract, such as during resistance training. They are small proteins or peptides that are also often produced in the body as inflammatory cytokines. Myokines help to regulate the metabolism and regeneration of muscle cells.[ref]
Myokines:
- Signal for the positive metabolic changes associated with exercise
- Initiate tissue repair
- Control the immune response to tissue damage
Different types of muscle fiber – fast twitch, slow twitch, etc – release different types of myokines. Genetic variants in the genes associated with myokines affect muscle recovery and growth and cause different results from resistance training.
Let’s take a closer look at some of the specific myokines released during resistance training.
IL-15 (interleukin 15): Myokine released when weight lifting
IL-15 is a myokine involved in muscle growth from resistance training. IL-15 is also a cytokine involved in inflammatory processes. It signals through a receptor called the IL-15 receptor alpha (IL15RA gene). IL-15 mRNA levels increase twofold within 24 hours after resistance training.[ref]
Genetic variants in the IL15RA gene are associated with increased muscle mass. (Included in genotype report section below.)
Animal studies show that reduced IL-15RA causes muscles to be more resilient to fatigue and the animals to be resistant to diet-induced obesity. With reduced IL-15 receptors, the animals can better use fatty acids for energy in their muscles. The knockdown of the IL-15 receptor causes the muscle cells to have an overall higher mitochondria content.[ref]
Myostatin: Negative regulator of growth
Myostatin is a negative regulator of muscle growth. It is part of the TGF-ß family of molecules and binds to the activin type 2 receptor (ACTRIIB) which decreases mTOR and AMPK (decreases growth-promoting proteins). [ref]
When myostatin levels are high, the satellite stem cells are inhibited and muscles don’t grow. Resistance training causes myostatin levels to decrease, thus allowing for muscle growth. Very high levels of myostatin cause muscle-wasting diseases, myopathy, and sarcopenia.[ref]
Genetic variants that cause lower levels of myostatin in humans generally result in increased natural muscle mass. (See genotype report section below.)
Double-muscled cattle are caused by a mutation in the myostatin gene that decreases myostatin production. Most cows aren’t bred to have the double myostatin mutation because it causes pregnancy problems and the need for more expensive feed.
Obesity and insulin resistance can increase myostatin levels. Prescription glucocorticoid medications also increase myostatin levels, which then causes mild muscle mass loss.[ref]
Follistatin: Myokine to increase muscle growth
Follistatin acts as an antagonist to myostatin. By binding to myostatin, follistatin can inactivate it, which then allows for muscle growth. During acute exercise, follistatin levels increase 5-7 fold which decreases myostatin and allows for muscle recovery and growth.[ref]
You may be thinking — why not just inject some follistatin to increase muscle growth? Well, follistatin has other roles in addition to antagonizing myostatin, and injecting it has multiple consequences. For example, FST is also a follicle-stimulating hormone inhibitor and is important in fetal development. Mutations that knock out the FST gene are lethal in utero. Animal studies show that the follistatin gene is also essential for ovarian egg production, and genetic mutations in follistatin cause infertility (and are thus rare and not passed on to offspring).[ref][ref]
Follistatin-like 3, also called follistatin-related gene protein (FLRG), is a follistatin homolog that can act as an antagonist to myostatin. Studies of follistatin-like 3 (FSTL3 gene) show that it has multiple roles in metabolic health as well as muscle growth. Animal studies show that reduced FSTL3 causes decreased fat mass and better glucose regulation, but it also causes some organ damage /changes. [ref]
Irisin: Exercise hormone and genetic variants
Irisin is a hormone released after exercise. It activates muscle satellite cells and increases protein synthesis. Irisin is synthesized from FNDC5, which is stimulated by PGC1α.[ref] PGC1α is encoded by the PPARGC1A gene. (Included in the section).
Building more muscle tissue: Signals and protein synthesis
When a muscle is stressed and has micro-trauma, it must rebuild and repair itself using amino acids to create muscle proteins. Thus, both protein synthesis and the signals for more protein synthesis are important for increasing muscle mass.
The role of mTOR in muscle growth
mTOR is a master regulator of protein synthesis and growth. It responds to nutrient levels and to mechanical overloading of muscles. mTOR is made up of two protein complexes, mTORC1 and mTORC2. Specifically, signals from the muscles when subjected to heavy loads during contraction cause an increase in mTORC1 signaling for hours after resistance training. mTORC1 then signals to increase the synthesis of proteins, lipids, and energy while limiting autophagy.[ref]
Muscle contraction uses energy in the form of ATP, and the available muscle ATP only lasts for a few contractions. Repeated or sustained muscle contractions then require more ATP production, which is usually from anaerobic glycolysis which produces ATP and lactate. The lactate causes the pH levels in the muscle cells to change, which triggers a signal to the brain and stimulates mTOR.[ref]
Genetic variants in the MTOR gene and the mTOR pathway affect muscle mass in response to training. (Included in the genotype report section)
IGF (insulin-like growth factor): Genetic variants and power athletes
IGF-1 and IGF-2 are growth factors that affect muscle mass. They are signals that communicate the physiological state of the body, and IGFs can be secreted by the liver when stimulated by human growth hormone (also called hGH or somatotropin).
IGF-1 increases skeletal muscle protein synthesis and muscle regeneration by activating satellite cells (muscle stem cells).[ref] IGF-2 is regulated by mTOR and amino acid sufficiency. IGF-2 signals the increase in skeletal muscle cell nuclei, which is important for increasing muscle mass.[ref] Variants in IGF2 are associated with power athletes and muscle mass. (Included in genotype report section below)
CNTF (Ciliary neurotrophic factor): Signaling growth
CNTF is a signaling molecule that promotes nerve and muscle growth. Animal studies show that CNTF treatment leads to increased myogenesis (new muscle cell formation) and decreased muscle atrophy signals. CNTF levels decline with age, and giving older animals CNTF improves muscle strength. The signaling molecule increases myoblast proliferation. A genetic variant that reduces the function of CNTF is linked to lower muscle mass in aging.[ref] (Included in genotype report section below)
Thyroid hormone regulation:
The thyrotropin-releasing hormone receptor, or TRHR, stimulates the release of TSH which causes the thyroid gland to release the thyroid hormone thyroxine. Thyroxine plays an important role in skeletal muscle development and maintenance. A deficiency of thyroid hormone, such as hypothyroidism, eventually causes muscle weakness. [ref][ref] Genetic variants in TRHR affect overall muscle mass, muscle strength in aging, and response to resistance training. (Included in genotype report section below.)
Cortisol is catabolic: Why chronic stress decreases strength
Studies show that there is an inverse relationship between cortisol levels and strength. Higher long-term cortisol levels correlate with lower grip strength.[ref] Essentially, high cortisol is catabolic – breaking down muscle.
Cortisol is released by the adrenal glands during acute stress, such as when you’re running away from a tiger that wants to eat you. As you run from the tiger, cortisol rises, signaling that nonessential bodily functions should be shut down and essential survival functions should be prioritized. Cortisol promotes energy to the muscles through gluconeogenesis so that you can run away from the tiger, but this energy is produced at the expense of muscle protein, leading to muscle catabolism in the long run. Thus, prolonged stress that increases cortisol can lead to decreased muscle mass.
Genetic variants in the cortisol receptor gene that alter cortisol binding are associated with lower muscle mass. (Included in genotype report section below)
Innervation and vascularization:
In order for muscles to grow, in addition to the increased size of the muscle fiber, the muscle tissue needs blood vessels to bring in oxygen and nutrients. It also needs to be innervated with extended nerve growth.
HIF1A:
HIF1A is a transcription factor that is activated by low oxygen conditions. HIF1A then increases the expression of genes related to energy metabolism in the cell. In muscle cells during resistance training, the oxygen and ATP are rapidly depleted during repetitions. HIF1A signaling helps to switch cellular energy production to adapt to low oxygen conditions in the muscle. The switch to anaerobic glycolysis in the muscle tissue is essential for exercise capacity. Genetic variants in HIF1A are related to the response to resistance training.
AGT (angiotensin):
Angiotensin is a peptide hormone that causes vasoconstriction to increase blood pressure. It helps to control blood pressure and electrolyte balance in the body through the renin-angiotensin system. Angiotensin is a precursor to the angiotensin II protein, which also acts as a skeletal muscle growth factor.
BDNF:
BDNF – brain-derived neurotrophic factor – acts as a myokine when released from muscle. Specifically, BDNF is released by satellite cells and is involved in the regeneration of damaged muscle. BDNF helps with cellular energy production by both enhancing lipid oxidation and improving glucose utilization. Resistance training increases circulating BDNF levels, and repeated training further increases BDNF levels.[ref]
In addition to acting in muscle cells to enhance repair, BDNF is also utilized in nerve growth and regeneration. Muscle hypertrophy requires new nerve growth, so increased circulating BDNF levels help with nerve growth in new muscles as well as benefiting the nervous system throughout the body. The increase in BDNF from exercise likely has multiple benefits for the whole body.[ref][ref]
BDNF levels increase similarly whether you do high-volume, low-weight training or low-volume high-weight training. Repeated training increased BDNF levels even more after a few weeks.[ref] The increase in plasma BDNF levels seems to be in response to an immediate drop in BDNF during exercise, and then a compensatory rise to restore and eventually increase levels a bit.[ref]
Note that while BDNF is also essential in brain function and related to mood disorders, circulating BDNF does not cross the blood-brain barrier.[ref]
Genotype report: Resistance Training
This section is divided up to show how different genetic variants affect aspects of muscle strength and growth:
- Variants related to muscle fiber
- Variants related to myokines
- Muscle protein synthesis: signals for growth
- Variants related to blood flow and innervation
Lifehacks: Maximizing strength from training
Setting goals: What’s realistic?
As we age, there is a slight loss of muscle mass starting in the late 20s (without resistance training). By age 80, the average individual will lose about 25% of their young adult muscle mass.
Consistent resistance training (e.g. weight lifting) can lead to a 5 to 20% increase in skeletal muscle mass within 2-4 months in people who are middle-aged or younger.[ref] Studies show that older adults can still gain muscle mass, but they do so at a slower rate than young or middle-aged individuals.[ref]
There are two main types of resistance training looked at in research studies:
- Hypertrophy training – maximizing muscle volume and growth by lifting heavy weights at fewer reps (e.g. bodybuilders)
- Strength endurance training – increasing time to exhaustion by increasing the lactate threshold (e.g. football, cycling, mountain climbing). This is usually done with more reps at lower weight.
Both types of training increase strength and muscle mass.[ref]
Which is better high load, low reps, or low load, high reps?
Study results vary on whether a low number of reps at greater than 60% of your maximum is better – or whether doing a lot of reps with a load that is less than 60% of your max will also work. There are also studies showing that varying between high-load reps and low-load reps is another alternative. [ref]
A study tried to answer this by comparing arm gains at different levels. The study involving lifting low levels of weights (20% of the one-repitition maximum) with one arm compared to s higher levels of weights (40%, 60%, 0r 80% of max) showed that all levels were effective in increasing muscle strength and size over six weeks. However, the 20% (lowest level) wasn’t as good as the 40%, 60%, or 80% of max.[ref]
Static stretching under load can also increase muscle mass along with flexibility.[ref]
Eccentric (lengthening) or concentric (shortening) contractions can also make a difference in the muscle response. Eccentric contraction is associated with greater initial damage repair, while concentric causes less acute damage. Looking at the transcription of genes within the muscle, eccentric contractions cause a greater acute signaling response for satellite cells, inflammation, and muscle fiber repair.[ref]
The ACTN3 Type IIX muscle fiber gives an advantage for powerlifting and bodybuilding. Hypertrophy training may be more effective for people with ACTN3 rs1815739 C/C or C/T genotypes, while individuals with the T/T genotype may find that strength endurance training (low load, high reps) is a better fit.Members: Your genotype for rs1815739 is —.
How often should you train?
Looking at studies on resistance training, a picture emerges that rest is needed for the recovery of specific muscle groups, but some kind of exercise on a daily basis is beneficial. For example, on days that you aren’t weight training, getting in another form of aerobic exercise may help to keep pro-resolving mediators high.
Here are the details of the studies:
Rest between muscle groups:
There is debate on the optimal frequency of training for a specific muscle group (e.g. biceps, triceps, legs). Recent studies show that training a muscle group 2x/week results in maximum hypertrophy. The rest period between muscle group training sessions needs to allow for protein synthesis to return to normal in those muscles. Studies show that 48-72 hours are needed, on average.[ref]
Resolving inflammation: Benefits of daily exercise of some kind
While resting specific muscle groups for 2 to 3 days in hypertrophy training is likely beneficial, regular moderate exercise also brings benefits for better production of pro-resolving mediators for the resolution of inflammation. Pro-resolving mediators are produced at the same time as inflammatory mediators (myokines) and help initiate the muscle repair process. For muscle growth, you need a balance of pro-resolving mediators and inflammatory signaling.
A recent study showed that daily moderate exercise upregulates the expression of the genes involved in the synthesis of specialized pro-resolving mediators (SPMs). The study compared the inflammatory response to resistance training in a group of runners to a matched control group that didn’t exercise daily. The results showed that the group that exercised daily (runners) had a much better, balanced inflammatory and pro-resolving mediator response to resistance training. Their production of pro-resolving mediators kicked in faster due to the early onset of ALOX15 gene expression.[ref] Another study in older adults showed that 2g/day of DHA plus EPA increased muscle mass gains and walking speed.[ref]
Read through the full article on specialized pro-resolving mediators for details on the genes involved in SPMs. The biosynthesis of SMPs utilizes DHA and EPA (omega-3 fatty acids found in fish oil). Here are your genetic variants related to SPMs:
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| FADS1 | rs174546 | T | -- | Lower FADS1 enzyme activity, benefit more from direct EPA/DHA intake |
| FADS2 | rs1535 | G | -- | Lower FADS1 enzyme activity, benefit more from direct EPA/DHA intake |
| ALOX5 | rs4987105 | T | -- | Decreased risk of type 2 diabetes, lower levels of C-reactive protein (good) |
| ELOVL2 | rs3734398 | C | -- | Decreased conversion of EPA to DHA |
| ALOX5AP | rs17216473 | A | -- | Increased risk of heart attack (population eating Western / high omega-6 diet) |
| ALOX12 | rs1126667 | A | -- | Slightly decreased risk of breast cancer, lower blood pressure (study group eating Western/ high omega-6 diet) |
| COX2 | rs4648310 | C | -- | Low DHA/EPA intake associated with a significantly increased risk of prostate cancer, but high DHA/EPA ameliorates the increased risk |
| COX2 | rs5275 | G | -- | Increasing intake of EPA/DHA reduces prostate cancer risk by 70% |
| GPR18 | rs3742130 | A | -- | SPM receptor; alters risk of IBD |
| CMKLR1 | rs1878022 | C | -- | Increased resolvin E1 receptor expression, reduced inflammation in obesity |
| GPR37 | rs149031046 | A | -- | Protectin D1 receptor mutation; possibly important in autism (rare) |
| LGR6 | rs10920362 | T | -- | increased risk of osteoporosis |
Optimizing thyroid function:
Thyroid hormone signaling is part of muscle building. The only way to know whether you have adequate thyroid function is to test your thyroid hormone levels (T3, free T4). Zinc, selenium, and iodine are important minerals for thyroid hormone production. While going overboard with the minerals can be detrimental, make sure that you are getting enough to be sufficient. [ref]
Eat enough for your activity level:
A study in female athletes showed that not consuming enough calories caused a reduction in lean muscle mass. The study showed that low energy intake (not eating enough for activity level) reduced thyroid function along with the loss of muscle.[ref]
Timing of eating:
A clinical trial on time-restricted eating where participants limited their eating window to 8 hours a day showed that it helped to improve thyroid function.[ref]
If you have the TRHR genetic variant associated with typical lean muscle and think you could have hypothyroidism, talk with your doctor or get full lab testing to check thyroid levels (more than just TSH).
Check your genetic data for rs7832552 (23andMe v5; AncestryDNA):
- T/T: greater lean muscle mass[ref] increased muscle protein formation[ref] less muscle loss in aging[ref]
- C/T: typical lean muscle mass
- C/C: typical
Members: Your genotype for rs7832552 is —.
Check your genetic data for rs16892496 (23andMe v5):
- A/A: typical
- A/C: greater lean muscle mass
- C/C: greater lean muscle mass[ref]
Members: Your genotype for rs16892496 is —.
Related article: Thyroid hormone levels, T3/T4 conversion, and your genes
Cortisol, stress, and ashwagandha:
Ashwagandha herbal supplements are often suggested for stress or anxiety due to its effect on cortisol. However, multiple studies show that this traditional Indian medicine increases strength gains from weight lifting. In men, ashwagandha also increases testosterone levels when taken in conjunction with strength training. In addition, a recent study showed that the active ingredient in ashwagandha increases muscle repair and activity.[ref][ref][ref]
Example study:
A double-blind, placebo-controlled clinical trial using 300 mg of ashwagandha root extract twice daily in men who weren’t regularly lifting weights showed significant results. After 8 weeks of resistance training, the group taking ashwagandha increased by 100 lbs in bench press – compared to 58 lbs in the placebo group. Arm size increased by about 1.5 inches more than the placebo group. [ref]
People with the highlighted variants may be more resilient to building muscle with high cortisol. If you do not have highlighted NR3C1 variants related to the cortisol receptor, consider your current stress level. Without the variants and with high cortisol, there may be more benefits to focusing on stress reduction and supplementing with ashwagandha (my interpretation).
Members: Your genotype for rs10482616 is —.
Members: Your genotype for rs4634384 is —.
Members: Your genotype for rs6189 is —.
Members: Your genotype for rs6190 is —.
Creatine for myostatin inhibition and mTOR activation:
Multiple studies show that creatine monohydrate supplementation increases muscle strength when combined with resistance training.[ref] For example, in healthy older adults aged 50-71, 0.1g/kg of creatine taken before resistance training increased lean muscle mass and decreased fat mass.[ref] In younger adults, creatine improves muscle mass and total body endurance from strength training compared to placebo.[ref]
Creatine monohydrate vs. creatine-hydrochloride:
A placebo-controlled clinical trial showed that both were effective for increasing muscle compared to placebo. There was no statistical difference in the benefits between the two types of creatine.[ref]
Genetic connections:
Creatine inhibits myostatin under certain conditions, and placebo-controlled trials show that it changes the follistatin/myostatin ratio.[ref][ref]If you do not have the highlighted (favorable for muscle) myostatin variant below, creatine may help by reducing myostatin expression and thus allowing more muscle growth.
Members: Your genotype for rs1805086 is —.
Creatine also enhances the activation of mTOR.[ref]
If you have the highlighted mTOR variant below, creatine may be even more beneficial.
Members: Your genotype for rs2295080 is —.
Recovery between sets: More reps or more weight?
In hypertrophy training (e.g. maximizing muscle size), the cross-sectional area of the muscle tissue increases in the fast type IIA fibers and slow Type-I fibers. This can be obtained by 6–12 repetitions with 70–85% of the one repetition maximum (1 RM). Often this is done in 2 to 3 sets, with 1–3 min rest intervals between the series. The short rest interval replenishes creatine phosphate but doesn’t give time for full metabolic recovery.[ref]
Strength endurance training uses more reps at a lighter weight, and the recovery time between sets is less than 90 seconds. The goal is not to increase the cross-sectional area of the muscle fibers, but instead to increase maximal aerobic power and time to exhaustion.
Amino acids and protein for muscle growth:
A recent meta-analysis of data from 49 studies showed that dietary protein supplementation increases muscle size and strength. The results showed that protein intake of more than 1.6g/kg/day doesn’t contribute to further gains.[ref] Protein alone is not a magic potion for muscles. Supplementing with protein while not doing resistance training doesn’t increase muscle mass and strength in healthy older adults.[ref]
Bodybuilders often consume whey protein either just before or right after a workout in order to provide the amino acids needed for building muscles.
I mentioned above that mTOR is the growth signal that turns on muscle protein synthesis after resistance training. In addition to training, another signal for mTOR is the levels of specific amino acids. Leucine, a branched-chain amino acid, is utilized for building muscle and also a signal for mTOR. Animal studies show that leucine levels are increased in the muscle after exercise and that an influx of leucine to the muscle cells (without exercise) can also stimulate mTOR.[ref]
Genetic connections:
If you have the highlighted variant, leucine may be even more beneficial.
Members: Your genotype for rs2295080 is —.
HMB for muscle growth:
HMB (hydroxymethylbutyrate or ꞵ-hydroxy ꞵ-methylbutyrate) is an active metabolite of the amino acid leucine. Studies show that it helps maintain muscle mass in older adults and may help build muscle during strength training. Essentially, HMB is anticatabolic, meaning it prevents the breakdown of muscle protein. Studies show that HMB increases gene expression of PPARGC1A, which plays a key role in the transformation of skeletal muscles. PPARGC1A shifts the muscle toward type I muscle fibers that have increased mitochondria and increased ATP production.[ref]
Increased muscle growth during strength training:
A couple of studies show that HMB helps to increase muscle mass in younger adults who do resistance training. The dosage used in the study was 3 g/day of HMB.[ref][ref] However, studies in older adults don’t necessarily show overall improvements in muscle mass. One study did show that thigh muscle improved with HMB plus training, but other muscle group improvements were not statistically significant.[ref]
Genetic connection:
Since HMB upregulates PPARGC1A, it may help people with the low PPARGC1A variant to supplement with HMB alongside resistance training.
Check your genetic data for rs8192678 Gly482Ser (23andMe v4, v5; AncestryDNA):
- C/C: typical (higher) PPARGC1A activity
- C/T: lower PPARGC1A activity; impairment of aerobic capacity; some advantage for strength training
- T/T: lower PPARGC1A activity; impairment of aerobic capacity[ref]; some advantage for strength training[ref]
Members: Your genotype for rs8192678 is —.
Caffeine plus resistance training:
Caffeine before a workout enhances velocity and power during training. It is also ergogenic, improving blood flow during the workout, and is linked to enhanced gains.[ref] A study specifically looking at the effects of the CYP1A2 genotypes along with caffeine for resistance training showed no differences in response.[ref]
Genetic connection:
A study found that individuals with the ADORA2A TT genotype, which heightens sensitivity to caffeine, have less inflammation when consuming caffeine one hour before a resistance training session.[ref] (This is the genotype that is also more susceptible to anxiety from caffeine, so take that into consideration as well.)
ADORA2A gene: adenosine receptor 2A
Natural supplements for increasing muscle mass:
Placebo-controlled clinical trials for resistance training show the following:
Eurycoma longifolia, also known as Tongkat ali, improves strength in men with androgen hormone deficiency (low-T). The trial lasted six months and involved men who were continuing to do resistance training. Supplemental Tongkat Ali improved peak torque for knee extension and knee flexion.[ref]
Urolithin A improved muscle strength and endurance in male athletes. The resistance-trained athletes consumed 1g/day of urolithin A for 8 weeks.[ref]
Arginine supplementation has been shown in middle-aged men to increase muscle mass a little. The dosage used was 5 g before a workout.[ref]
Capsaicin supplement (12 g) improved number of reps per set in healthy resistance-trained young men.[ref]
Related articles and topics:
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