Carnitines (Including l-Carnitine, Acetyl- Carnitine, and Proprionyl-Carnitine)

Luísa C. Roseiro and Carlos Santos

Instituto Nacional de Investigação Agrária e Veterinária, I.P., Oeiras, Portugal

INTRODUCTION

Carnitine (β-hydroxy-γ-trimethylaminobutyrate), a nonessential organic nutrient, is a quaternary ammonium compound, naturally occurring in nature. It is found in greater concentration in all animal species, and in numerous microorganisms and plants (Vaz and Wanders, 2002). l-carnitine has a number of important roles in intermediary metabolism. l-carnitine is involved in the transport of activated long-chain fatty acids from the cytosol to the mitochondrial matrix, where β-oxidation takes place. Other physiological roles of carnitine include modulation of the acyl-CoA/CoA ratio (Carter et  al., 1995; McGarry and Brown, 1997), storage of energy as acetyl-carnitine (Bremer, 1983; Carter et  al., 1995), and the modulation of toxic effects of poorly metabolized acyl groups by excreting them as carnitine esters (Duran et  al., 1990; Rebouche, 1996). Aside from assisting in fatty acid transport, carnitine has an antioxidant activity, protecting various cells against oxidative injury (Ribas et al., 2014). In animal tissues, l-carnitine is maintained by absorption from dietary sources, endogenous synthesis, and efficient tubular reabsorption by the kidney. The main sources of dietary l-carnitine include animal products, particularly red meat with 500–1200 mg/kg, followed by fish, chicken, and dairy products, containing 16–64 mg/kg. On the other hand vegetables, fruits, and grains contain very little carnitine amount (<0.5 mg/kg). Unfortunately, only 60%–70% of available carnitine is absorbed from food sources and its content can be depleted if meat is cooked at high temperature over an open flame (Bloomer et  al., 2013). Although animals obtain carnitine primarily from their diet, most mammals are capable of synthesizing carnitine endogenously. Synthetized from essential amino acids, lysine and methionine, l-carnitine is involved in reversible transesterification reactions with distinct chain length acyl-CoAs, catalyzed by carnitine acyltransferases of distinct chain length specificities (carnitine acetyl-, octanoyl-, and palmitoyltranferases) and in the transportation of activated fatty acids through membrane systems within the cell, particularly into the mitochondrial matrix (long-chain fatty acid oxidation, known as mitochondrial β-oxidation) (Kerner and Hoppel, 2013). This latter process represents the repetitive oxidative cleavage of long-chain fatty acids into two carbon units, acetyl-CoA, which is further oxidized for energy production. In addition to l-carnitine, the biologically active form, a variety of specific carnitine forms have been studied. Acetyl, propionyl, tartrate, and fumarate are some of the carnitine salts investigated with specific goals. Acetyl-l-carnitine has the ability to cross the blood–brain barrier and has been used for enhancing cognitive function, memory, and mood (Inano et  al., 2003). Ho et  al. (2010) reported that l-carnitine l-tartrate has an important impact in selected markers of exercise recovery. Synthetized by the esterification of propionic acid and carnitine, the propionyl-l-carnitine (PLC) is a novel form of carnitine with multiple physiological roles which has recently been used as a food supplement in the form of glycine propionyl-l-carnitine (GPLC) (Mingorance et al., 2011).

CARNITINE

The daily requirement of carnitine by humans is met by endogenous synthesis and dietary intake, mostly from meat and meat products. In the former case, protein bound lysine is first methylated to trimethylysine (TML) using s-adenosylmethionine. Availability of the intermediate TML limits carnitine biosynthesis with most TML stored in the body

Biosynthesis of L-carnitine

being located in skeletal muscle protein. Following proteolytic liberation, free TML is converted by multiple reactions to butyrobetaine (BB) (not in cardiac and skeletal muscle), the ultimate carnitine precursor. In such process, lysine supplies the carbon skeleton to the carnitine molecule (Fig. 2.5.1) and, in turn, methyl groups come from methionine residue (Pekala et al., 2011). The N-metylation of lysine residues observed in many proteins (myosin and actin for example) is a kind of translational modification with such reaction being catalysed by a specific methyltransferase. s-adenosyl-l-methionine is a cosubstract with chemically reactive methyl groups attached to the sulfur atom, which makes it a methyl-group donor.
The lysossomal hydrolysis of proteins containing TML releases the TML residues, which are then hydroxylated by mitochondrial dioxygenase TML (TMLD) to 3-hydroxytrimethyllysine (HTML). The next stages involve HTML cleavage to glycine and 4-trimethylaminobutyraldehyde (TMABA) catalysed by HTML aldolase (HTMLA) and the dehydrogenation of TMABA to give BB catalysed by TMABA dehydrogenase (TMABA DH). Although most tissues are capable of synthesizing BB, the hydroxylation of BB to carnitine is restricted to the liver and, to a lesser extent, in the kidneys and the brain (Berardi et al., 1998; Kerner and Hoppel, 2013), requiring the iron ion and ascorbate as cofactors (Paik et al., 1977; van Vlies et al., 2006).


Free l-carnitine, absorbed from dietary intake or synthesized in the liver and kidneys, reaches the blood stream and is then taken up by other tissues. Since the carnitine concentration in tissues is generally higher than in plasma, its body distribution is determined by a series of systems of active transport against a concentration gradient, an independent efflux process, and an exchange mechanism, specific to each tissue type. Under physiological conditions, plasma carnitine concentration is maintained within a narrow range by a modest rate of inner carnitine synthesis, dietary intake, and efficient management by the kidneys (Kerner and Hoppel, 2013). Carnitine is not metabolized in the human body, being filtered at the renal glomerulus with about 85% of it being reabsorbed by the proximal tubules (Rebouche and Engels, 1984).
Less than 2% of the absorbed carnitine is excreted in urine or bile (Pekala et al., 2011), in the form of l-carnitine, acetyl l-carnitine, and other acylcarnitine esters (Rebouche and Engels, 1984). Nevertheless, longer chain carnitine esters are absorbed less than the other carnitine forms. Because tissues such as heart, muscle, liver, and kidney are very dependent on the energy generated by β-oxidation, it is crucial they have sufficient amounts of carnitine.

DIETARY SOURCES AND INTAKE OF l-CARNITINE

The carnitine reserves consist of nonesterified molecules (free carnitine) and multiple acylcarnitine esters (forms bounded
to different fatty acids). About 99.5% of body carnitine is intracellular, while circulating plasma carnitine accounts for only 0.5%. Daily urinary carnitine excretion equals the sum of dietary absorption and endogenous synthesis (about 400 μmol/ day) (El-Hattab and Scaglia, 2015; Rebouche, 1992; Stanley, 2004).
The body carnitine level is maintained by absorption from the diet, synthesis, and renal reabsorption. At normal physiological
conditions, renal carnitine reabsorption is very efficient (90%–99% of the filtered load) being equal to the normal plasma carnitine concentration (approximately 50 μmol/L). Thus, when carnitine increases in the plasma circulation, the efficiency of its reabsorption decreases and its clearance increases, which results in a rapid decline of carnitine concentration to its baseline. Therefore, as the dietary intake of carnitine varies, urinary carnitine excretion also varies to keep plasma carnitine within the normal range (Ramsay et al., 2001). Under normal circumstances, an adult (about 70 kg) can synthetize from 11 to 34 mg of l-carnitine each day (160–480 μg/kg body weight). This amount can be insufficient when living is stressful or physically exigent, namely in the case of men undertaking advanced sports training or athletes. About
75% of the carnitine present in the body is obtained from the diet (Flanagan et al., 2010). l-carnitine is mostly present in meats and dairy products and almost absent in vegetables (Rebouche et al., 1993). Among foods from animal origins, lamb and beef have higher l-carnitine contents than fish, pork, and poultry, followed by, in decreasing order, whole milk and cottage cheese. In fruits and vegetables, only avocado and asparagus have noteworthy amounts of carnitine (Pekala et al., 2011). Since carnitine is more concentrated in animal products, strict vegetarians, and lacto-ovo vegetarians, get very little carnitine from their diets. The rate of l-carnitine biosynthesis in vegetarians is estimated to be around 1.2 μmol/kg of body weight per day while omnivorous humans ingest 2–12 μmol/kg of body weight per day, which represents 75% of carnitine sources in the body (Vaz and Wanders, 2002). Regular supplementation is sometimes recommended but, in theory, makes sense only in individuals performing acute physically stressful tasks (muscle carnitine faster depletion). The bioavailability
of oral carnitine dietary supplements is only in the order of 14%–18% of the dose (Rebouche, 2004).

CARNITINE FUNCTIONS

There are two forms of carnitine: l-carnitine (biologically active) and d-carnitine (inactive). Aside from the assistance in fatty acid transport, l-carnitine and its derivative salts (fumarate, acetyl, tartrate, propionyl, etc.) show antioxidant activity (Calo et al., 2006) and may participate in improving cognitive function (acetyl-l-carnitine) (Inano et al., 2003), exercise recovery (l-carnitine l-tartrate), (Ho et al., 2010) and nitric oxide (NO) production (PLC; GPLC) (Mingorance et al., 2011).
The main function of carnitine in intermediary metabolism is the transport of long-chain fatty acids from the cytosol to the mitochondrial matrix. l-carnitine is yet involved in the transfer of peroxisomal β-oxidation products (acetyl-CoA) for Krebs cycle oxidation or in the modulation of the acyl-CoA/CoA ratio, storage of energy as acetyl-carnitine, and regulation of the toxic effects of poorly metabolized acyl groups by excreting them as carnitine esters (excretion in urine) (Pekala
et al., 2011).

CELLULAR UPTAKE AND ACTIVATION OF LONG-CHAIN FATTY ACIDS

Long-chain fatty acids represent an unequivocal source of energy production for many organs, mainly for muscle and liver, but since most tissues have only residual levels of storage lipids, they depend on a continuous supply of fatty acids from adipose tissue following mobilization by lipolysis and transport in the blood bound to albumin. The fatty acids uptake by tissues is a process mediated by transport proteins located in the plasmatic membrane and once within the cell they are then bound to proteins existing in considerable amounts in the cytosol. Depending on the tissue demand for energy, fatty acids are transformed to triglycerides and stored for further oxidation in mitochondria. Before being sent into storage or oxidation, fatty acids are first activated to acyl-CoA esters, with such reactions being catalyzed by long-chain acyl-CoA synthetase.
Cytosolic long-chain acyl-CoA is impermeable to the mitochondrial membranes and, in general, carnitine works as a carrier for the acyl groups. Long-chain fatty acid acyl groups are transported exclusively as carnitine esters by translocase, which constitutes a transmembraneous protein located in the inner mitochondrial membrane. The impermeability of the mitochondrial membranes, particularly the outer membrane, can be overcome by a voltage-dependent mechanism, involving an anion-selective channel, called mitochondrial porin, which regulates the permeability of this membrane to ions and metabolites (Kerner and Hoppel, 2013).
The mitochondrial carnitine system plays a crucial role in the β-oxidation of long-chain fatty acids through their transport into the matrix, involving the malonyl-CoA-sensitive carnitine palmitoyltransferase-I (CPT-I, located in the outer membrane), the carnitine:acylcarnitine translocase (CACT) (an integral inner membrane protein), and carnitine
palmitoyltransferase-II (CPT-II, localized on the matrix side of the inner membrane) (Fig. 2.5.3). CPT-I transfers activated long-chain acyl residues from acyl-CoA into carnitine. The resulting long-chain acylcarnitine esters are transported over the inner mitochondrial membrane via an integral inner membrane protein, CACT. Following the
translocation of long-chain acylcarnitines into the mitochondrial matrix, the carnitine esters are converted to their respective intramitochondrial CoA esters by CPT-II, thus completing the carnitine-dependent uptake of activated fatty acids (Longo et al., 2016). Finally, the acyl-CoA undergoes β-oxidation with a release of energy in the ATP form. Fatty acid β-oxidation is a multistep process by which the activated long-chain fatty acids are broken down, with each cycle
resulting in the removal of two carbon atoms from the fatty acyl residue in the form of acetyl-CoA (Kerner and Hoppel, 2013; Pekala et al., 2011).
The influence of l-carnitine on an exercise-altered metabolism may be explained by its relation to acetyl-CoA. Acetyl- CoA is a common product of glycolysis and fatty acid l-carnitine β-oxidation. Increased levels of acetyl-CoA can interfere with the conversion of pyruvate into acetyl-CoA by suppressing the l-carnitine-mediated increase (Kerner and Hoppel, 2013).

Main functions of carnitine in the brain, liver, and muscle cells under physiological conditions

Role of L-carnitine in the transport of long chain fatty acid into the mitochondria. CACT, carnitine-acylcarnitine translocase; CAT, carnitine acetyltransferase; CPT I, carnitine palmitoyltransferase I; CPT II, carnitine palmitoyltransferase II

l-CARNITINE’S ANTIOXIDANT ROLE DURING OXIDATIVE STRESS

Despite the role of l-carnitine in fatty acid transport, many studies have suggested this compound as an antioxidant (Lohninger et al., 2005; Ribas et al., 2014; Surai, 2015). This role of carnitine seems to be an apparent contradiction, since l-carnitine increases the metabolism of fatty acids facilitating the formation of reactive oxygen species (ROS) by the electron transport chains of mitochondria. However, it has been reported that l-carnitine determines the formation of NO (Brown, 1999), activating oxidative damage defense enzymes (Kremser et al., 1995) and superoxide dismutase (SOD) as well as catalase against 3-nitropropionic acid-induced neurotoxicity (Kremser et al., 1995). According to the literature review we can conclude that there are several important mechanisms in the antioxidant action of carnitine (Bloomer et al., 2013; Kolodziejczyk et al., 2011; Ribas et al., 2014; Sung et al., 2016; Surai, 2015). l-carnitine is shown to directly scavenge free radicals and it can chelate transition metals (Fe2+ and Cu+), preventing their participation in ROS formation (Surai, 2015). l-carnitine decreases free radical formation by inhibiting specific enzymes (e.g., xanthine oxidase and
NADPH oxidase) responsible for free radical production, which have a high biological relevance in various stress conditions.
In addition, carnitine participates in maintaining the integrity of mitochondria, including the electron-transport chain of mitochondria, in stress conditions. Indeed, carnitine can be considered as a mitochondria-specific antioxidant, responsible for the maintenance of mitochondria integrity and regulation of ROS production and ROS signaling (Surai, 2015). The protective effect of l-carnitine and its derivatives on the antioxidant systems of the body is also shown in various models of oxidative stress/toxicity caused by a variety of toxicants and neurotoxic agents (Surai, 2015).


Determined under in vitro conditions, the antioxidant capacity of l-carnitine seems to be dependent on concentration, behaving similarly to α-tocopherol and trolox administered at a concentration of 30 μM, through scavenging effects (Gülçin, 2006). l-carnitine administration during exercise is expected to boost the activity of endogenous antioxidants, delaying fatigue by removing ROS (Wickens, 2001). In a study using human blood samples it was concluded that l-carnitine provided protective effects, including suppressing peroxynitrite-induced peroxidation and decreasing low molecular–weight thiols, glutathione and cysteine, through the oxidation of the arachidonic acid cascade and antioxidant mechanisms (Malaguarnera et al., 2009; Saluk-Juszczak et al., 2010).
Low-density lipoprotein (LDL) cholesterol is one of the major risks for cardiovascular diseases (Lembo et al., 2000), with the oxidized form being an essential element in atherosclerotic plaque formation (Boullier et al., 2001; Steinberg, 1997). Oral administration of l-carnitine in patients with diabetes with increased oxidized LDL levels reduced oxidized LDL, indicating that l-carnitine can effectively control diseases induced by ROS increase. Thus, l-carnitine is effective in a relatively wide range of ROS and ROS-induced lipid peroxidation, preventing inflammation by scavenging mechanisms. However, the precise
mechanism by which l-carnitine acts as an antioxidant has not yet been confirmed (Boullier et al., 2001).
The increase of ATP synthesis by the electron transport chain and the production of ROS associated with physical exercise, promotes reduced muscle contraction, inducing fatigue and loss of performance. The administration of l-carnitine improves exercise performance since it accelerates ATP synthesis by fatty acid metabolism, removes and mutates ROS, and activates stabilization of endogenous antioxidants, improving muscle contraction efficiency and delaying fatigue (Sung
et al., 2016).

OTHER ROLES OF CARNITINE IN METABOLISM

l-carnitine plays a crucial role in the maintenance of the acetyl CoA/CoA ratio in the cell during high-intensity exercise, which produces large amounts of acetyl CoA (Hoppel, 2003; Pekala et al., 2011). Such an increase inhibits the pyruvate dehydrogenase complex and consequently the rise of lactate. By reacting with acetyl-CoA carnitine suppresses the accumulation of lactic acid, forming acetyl carnitine and CoA, enhancing performance under high-intensity exercise. In some other metabolic conditions, for example, ischemia, fasting, and acute stress, characterized by increased pyruvate dehydrogenase activity and fatty acid supply from activated lipolysis, the capacity to oxidize acetyl-CoA may be exceeded, leading to an accumulation of acetyl-CoA and short chain acyl-CoA esters obtained from the degradation of branched-chain amino acids in skeletal muscle (Pekala et al., 2011).
Carnitine is also an activator of carbohydrate metabolism by promoting pyruvate oxidation associated with the decrease in acetyl-CoA content (Pekala et al., 2011).

SUPPLEMENTATION OF l-CARNITINE IN SPORTS NUTRITION

The performance enhancement of l-carnitine on exercise is due to glycogen-sparing effects, reduction in the accumulation of lactate, and an increase in fatty acid metabolism. However, the increased accumulation of ROS deteriorates the force of muscle contraction as well as the oxidation level of plasma components. Ergonomic aids in sports nutrition include dietary antioxidants such as vitamin C and E to improve exercise performance, by reducing oxidative stress (Bryant et al., 2003; Snider et al., 1992; Sung et al., 2016). Based on the few studies carried out so far, it is difficult to determine the optimal dosage of l-carnitine as well as its administration period. l-carnitine is probably beneficial when muscular function is impaired in metabolic diseases, but has little or no effect in healthy individuals. While exercise increases the metabolic rate, it can result concomitantly in excessive ROS formation. In such cases l-carnitine aids by reducing oxidative stress by attenuating ROS and accelerating endogenous antioxidant activity.

POTENTIAL EFFECT OF CARNITINE AS A THERAPEUTIC AGENT

It is well known that l-carnitine and its esters are able to improve metabolic functions, inclusively under pathological conditions (Nagesh et al., 2011; Ramsay and Zammit 2004; Shenk et al., 2009; Zhang et al., 2010).
The supplementation of l-carnitine seems to benefit conditions such as anorexia, chronic fatigue, coronary vascular disease, hypoglycemia, male infertility, and muscular myopathies, among others (Pekala et al., 2011). Clinical studies have demonstrated that l-carnitine favorably modulates oxidative stress through preventing membrane fatty acid peroxidation
(Malaguarnera et al., 2009). According to Sayed-Ahmed et al. (2001) l-carnitine prevented the progression of atherosclerotic lesions. The protective effects of l-carnitine against damage to the heart, caused by diabetes-induced alterations, and additional ischemia have been described by Schneider et al. (2005). l-carnitine may be an important agent in the protection of myocardial alterations in diabetes with additional ischemia, since it stabilizes mitochondrial and cellular functions and acts through its antioxidant or radical scavenging potential (Kolodziejczyk et al., 2011).
As a food supplement, carnitine is mostly available as l-carnitine or bound to either acetic or propionic acids (acetyl l-carnitine and propionyl l-carnitine, respectively). Acetyl-l-carnitine (ALC) is produced from l-carnitine and acetyl-CoA in mitochondria by carnitine O-acetyltransferase, and transported to the cytoplasm where it is converted back to l-carnitine and acetyl-CoA. Several studies have suggested that ALC may play a neuroprotective role in hypoxic-ischemic brain injury (Virmani and Binienda, 2004; Wainwright et al., 2006; Zanelli et al., 2005). ALC serves as a source of acetylcholine and l-glutamate, and also contributes to energy-producing reactions. The ALC appears to be the best form to use for brain disorders (Alzheimer’s disease) while propionyl l-carnitine seems to be more effective for heart and peripherical vascular diseases. PLC is a naturally occurring derivative of carnitine that plays an important role in the metabolism of both carbohydrates and lipids, leading to an increase of ATP generation. PLC is transported, into the cell, to the mitochondria, where it is transformed into free carnitine and propionyl-CoA. The latter is converted into succinyl-CoA and finally to succinate, which is involved in the citric acid cycle. PLC is also a potent antiradical agent and thus may protect tissues from oxidative damage. PLC has been demonstrated to exert a protective effect in different models of both cardiac and endothelial dysfunction, to prevent the progression of atherosclerosis, and, more recently, to improve some of the cardiometabolic alterations
that frequently accompany insulin resistance (Mingorance et al., 2011). PLC is a novel carnitine molecule known in the dietary supplements sector as GPLC. Both PLC and GPLC have been reported to improve the physical condition, with increased nitric oxide metabolites (Bloomer et al., 2007, 2009).

CONCLUSIONS

l-carnitine is an amino acid derivative, available in several forms, which possesses multiple physiological properties. The main known functions of l-carnitine are the transport of activated long-chain fatty acids from the cytosol to the mitochondrial matrix, the modulation of the acyl CoA/CoA ratio, storage of energy as acetyl-carnitine, the modulation of the toxic effects of poorly metabolized acyl groups, and its antioxidant activity. Several studies have demonstrated the antioxidant properties for l-carnitine in different pathologies such as diabetes, hypertension, renal and liver diseases, and also in neurodegenerative conditions. l-carnitine, as a nutritional supplement, has been considered a promising candidate for the prevention and treatment of oxidative alterations in many metabolic diseases. Concerning the optimal dosage and route
of administration, additional, well-controlled studies are still needed to clarify safe, practical, and therapeutic guidelines.
Acetyl l-carnitine and propionyl l-carnitine, the main esterified forms of l-carnitine, have been studied in terms of its role in enhancing cognitive function, exercise recovery, and in the heart and peripheral vascular system. l-carnitine and/or its esterified forms seem to play an important role in the metabolism of the human body when it can be used as a therapeutic agent. l-carnitine supplementation may be useful not only to prevent tissue deficiency, but also to avoid oxidative damage,
secondary to an increased production of ROS. Considering the ability of l-carnitine to easily cross the blood–brain barrier, l-carnitine supplementation may also be beneficial in preventing neurological damage derived from oxidative injury.
However, further studies are required to better explore this potential role.

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Best Types of Supplements for Losing Weight

Everywhere you turn there is a new diet, new workout, or new pill promising weight loss success. Quick results can be very tempting, but they often only provide short-term success.

So, what can a person do to achieve long-term weight loss success? This can be a complex question since not one weight loss program or product is going to be fitting for every person.

This is because people with different health backgrounds such as those with diabetes, kidney disease, and/or heart disease will all have different nutrient needs.

Those with diabetes will need to limit carbohydrate intake, while those with heart disease will have to limit sodium intake. And if you have kidney disease, you may have to limit potassium, phosphorus, and sodium. So, in these cases, weight loss meal planning may be a little more complicated than just calorie counting or measuring your macros.

Those people who are known to have the greatest weight loss success share common habits. The National Weight Control Registry, established in 1994, have been collecting data from people who have lost and kept off 30 pounds or more for at least one year.

Common habits of many of these people include eating breakfast every day, weighing themselves at least once a week, watching less than ten hours of television each week, and exercising about an hour each day.

Although diet and exercise interventions can provide weight loss success for the long-term, sometimes it is not enough. Research shows that in some cases adding a weight loss medication or supplement can help people attain long-term weight loss success.

Safety concerns may be preventing some from trying a weight loss supplement. Therefore, read below for a list of safe weight loss support supplements that could help you reach your weight loss goals.

Key Supplements for Losing Weight

Caffeine

When you think of caffeine, you might think of coffee, cola, and jittery hands. However, caffeine can actually be an ally in your weight loss journey if used properly. Caffeine is a bitter substance found in coffee beans, tea leaves, kola nuts, and cacao pods.

This compound is found in food and drink products such as coffee, tea, cola drinks, and chocolate, respectively. However, some caffeine is also found in a synthetic form in some energy drinks and over-the-counter medications.

Caffeine is an effective compound when it comes to weight loss since it helps increase energy expenditure and decrease energy intake. A meta-analysis of studies showed that for every doubling in caffeine intake, the average reduction in weight, body mass index, and fat mass increased two-fold. Also, one study found that those who consumed more coffee and caffeinated drinks were more likely to maintain their weight loss.

Caffeine consumption is generally safe for most people, as long as you don’t drink too much. Experts suggest limiting caffeine intake to no more than 400 milligrams a day. Those with pre-existing heart conditions may want to limit their caffeine intake to even less since acute intake of caffeine can slightly increase blood pressure.

Also, those who are pregnant should limit caffeine intake as much as possible since it can increase risk of miscarriage and stillbirth.

So, when consumed in moderation, as long as you are not included in these at-risk groups, caffeine can be a great way to help boost your weight loss efforts. If you notice, disturbances in sleep, headaches, or anxiety, then reduce or stop your intake of caffeine and contact a qualified healthcare provider.

L-Carnitine

Derived from an amino acid, this compound has extensive research showing its effectiveness in weight loss support. Even though the body makes carnitine, it is also found in animal products like meat, poultry, seafood, and dairy products.

Inside the cells in the body, carnitine plays a role in the breakdown of fats. A study of older adults showed that L-carnitine can provide a variety of health benefits. Besides increasing muscle mass, L-carnitine revealed the ability to decrease body weight and reduce physical and mental fatigue.

Another study analyzed a variety of different studies looking at L-carnitine and weight loss effects. Study results show that those who took L-carnitine supplements lost significantly more weight compared with control groups. However, the health benefits of L-carnitine extend beyond just weight loss.

A study of women with polycystic ovary syndrome looked at the impact of L-carnitine on a variety of health markers. Study results show that after 12 weeks of L-carnitine supplementation, these women not only lost weight and inches off their waist and hips, but also had improvements in their blood glucose control.

Carnitine supplements are thought to be safe at up to 2 grams a day for one year or up to 4 grams of day for 56 days. Side effects may include nausea, vomiting, diarrhea, abdominal cramps, and fishy body odor.

Since certain antibiotics and anticonvulsant medications may interact with L-carnitine, it is important to ask your healthcare provider before starting this supplement.

Chromium

This mineral is seen often in weight loss products, so it’s no surprise that it makes the list for best weight loss support supplements. Chromium, in its trivalent (+3) form, is needed in trace amounts by humans, with adequate intakes ranging between 20 and 35 micrograms for most adults.

This mineral is found in rich amounts in broccoli, grape juice, mashed potatoes, and whole-wheat English muffins, but most other foods contain less than 2 micrograms chromium per serving. Therefore, supplementation would be beneficial for most people if these foods are not in your daily diet.

A review of current studies on chromium and weight loss show that chromium supplementation produces significant weight loss results. These were small studies, however, so these study results warrant further research on this promising mineral.

More recent studies looked at the effect of a supplement that includes cinnamon, carnosine, and chromium on weight loss. Study results show that after four months of this supplement, overweight or obese pre-diabetic subjects saw decreased fasting plasma glucose and increased fat-free mass.

These results show that chromium can provide extensive health benefits to not only those wishing to lose weight, but also to those wishing to improve their blood glucose levels. Although these effects were also seen in some research on women with polycystic ovary syndrome, longer term studies are warranted to see the full benefit chromium could have on this population.

Few serious side effects have seen in relation to chromium intake. Because of this, no Tolerable Upper Intake Level (UL) has been confirmed. However, chromium may interact with some medications, so you should ask your doctor before starting a daily regimen of this supplement.

Glutamine

This non-essential amino acid is not only an important energy source for many cells in the body but has also proved itself to be an effective weight loss support supplement. Glutamine is involved in many metabolic processes in the body, therefore is abundant throughout the body.

Animal studies show that glutamine can help improve energy balance in the body. It does this by helping to improve blood glucose levels and intestinal glucose production in the body, which contribute to maintain glucose balance. These metabolic factors are important since they typically correlate with improved ability to lose weight.

Another study looked at obese female patients and the impact of glutamine supplementation on weight loss. Study results show that body weight and waist circumference significantly declined, while metabolic markers like insulin resistance was slightly improved.

Furthermore, other research looked at the effect of glutamine on the gut microbiome as one possible reason for its success as a weight loss support supplement. Results of this study show that as compared with alanine supplementation, glutamine supplementation reduced the Firmicutes to Bacteroidetes ratio. This in turn resembled weight loss programs already seen in the literature that show that higher ratios of these bacterium were linked with obesity.

Glutamine supplementation is generally safe for most people. Some side effects may include nausea, vomiting, abdominal pain, headache, or rash, to name a few. Also, glutamine may interact with some medications, so be sure to talk to your healthcare provider before you start to take this supplement.

Green Tea

Used in China and Japan for thousands of years for medicinal purposes, green tea, derived from the Camellia sinensis plant, has shown effectiveness as a weight loss support supplement. Often consumed as a tea, green tea can also be ingested in its extract form.

The active ingredient in green tea is the catechin EGCG, or epigallocatechin gallate. Research shows that intake of EGCG can enhance exercise-induced fat oxidation.

One study looked at the effect of drinking Matcha green tea, which contains catechins and caffeine, before a walking regimen. Study results show that those who consumed the tea had lower respiratory exchange ratios and enhanced fat oxidation.

Respiratory exchange ratios (RER) are typically used to measure exercise tolerance, so a lower RER after exercise would indicate a higher exercise tolerance. Also, fat oxidation, or fat burning, would indicate greater energy utilization. Therefore, this study suggests that green tea could help optimize the health benefits of exercise.

Furthermore, another study looked at the effects of a supplement containing green tea, capsaicin, and ginger on weight loss. Study results show that those overweight women who took the co-supplements for eight weeks had beneficial effects on not only weight loss and body mass index, but also on markers of insulin metabolism and the antioxidant glutathione.

As far as safety goes, green tea is believed to be safe for most people when consumed in moderate amounts. Research shows that a safe level intake of green tea is 338 milligrams of EGCG each day as a solid bolus dose, while an observed safe level (OSL) of 704 milligrams EGCG/day may be safe for tea preparation intake. Liver problems have been observed in a small number of people who took concentrated green tea extracts.

However, for the average person, green tea could be a great way to boost antioxidants and enhance weight loss support.

Selenium

This trace element, which is nutritionally essential for humans, plays roles in thyroid metabolism, DNA synthesis, and protection from oxidative damage.

Most adults are recommended to consume about 55 micrograms selenium each day. Although it is found in foods such as Brazil nuts and yellow fish tuna in rich amounts, since these foods are not commonly consumed daily by many, then selenium supplementation could be beneficial for most people.

Research shows that selenium supplementation could help support weight loss. One study looked at the impact of selenium intake on body fat. Study results show that obese individuals had the lowest selenium intakes, and that high selenium dietary intake was linked to a beneficial body composition profile.

Besides weight loss support, selenium may also benefit metabolic health. One study looked at the impact of selenium intake on insulin resistance. Study results show that higher dietary intake of selenium was linked to lower levels of insulin resistance. However, the benefit of selenium on insulin resistance stopped at intakes above 1.6 micrograms per kilogram per day.

Selenium can interact with some medications like certain chemotherapeutic agents like cisplatin. Therefore, you should always let you doctor know about any new supplements you may be taking. However, for most people, selenium intake is generally safe in moderation with the tolerable upper intake of this supplement being 400 micrograms a day for most adults.

Whey Protein

This powdered protein supplement is best known for its presence in fitness shakes and protein bars to provide a portable source of protein when you are on the go or working out. However, this supplement has also proven itself to be an effective weight loss support supplement.

Whey protein is one of the primary proteins found in dairy products that can be added to liquids and soft foods to improve nutrient intake and/or athletic performance. Research shows that whey protein supplementation helps to improve whole body anabolism, which involves the building up of muscle mass and bone. It has also been shown to improve muscle recovery after exercise and improve body weight, total fat mass, and some heart disease risk factors in overweight and obese patients.

Also, when compared to intake of carbohydrates or a combination of carbohydrates and proteins, whey protein supplementation may increase abdominal fat loss and fat-free mass. Other related research shows that when combined with a low-calorie diet, whey protein supplementation can assist in maintaining lean body mass and enhancing fat loss.

Whey protein is generally safe for most people to consume. However, those with a dairy allergy or sensitivity should not consume whey protein as it may cause gastrointestinal discomfort, and those taking certain antibiotics or osteoporosis drugs may experience drug interactions when taking whey protein.

It is also important to note that those with lactose intolerance may be able to tolerate lower lactose formulas of whey protein such as whey protein isolate versus whey protein concentrate.

Therefore, for most people whey protein can be a nutritious, portable protein that can support weight loss. Added to smoothies, water, or other recipes, whey protein can be a delicious way to enhance your weight loss success.

Summary

No matter what your weight loss goals are, or what your health background is, a healthy diet and staying active is key to losing weight and keeping it off. However, because everyone has different health backgrounds, nutrient needs may be different. Not to mention that not all people may find weight loss success with diet and exercise alone. That is why a weight loss supplement can help support weight loss efforts for some people.

The above supplements have evidence-based research to support their effectiveness, but keep in mind that just because one supplement works well for one person, that doesn’t mean it will work for everyone. And remember that you will receive best results from any weight loss support supplement by also maintaining a healthy diet and exercise program.

When choosing a weight loss support supplement, it is important to consider safety and effectiveness. Since some weight loss supplements in the past have had serious side effects such as heart health risks, it is important to check the safety statistics on the supplements you are researching. It is also important to check and make sure no ingredients in a weight loss supplement interact with any medications or other supplements you are taking.

Once a supplement has passed the safety test, such as those listed above, then you can give it a try. It is best to stick to supplements that have evidence-based research that report its effectiveness, so you don’t waste your time and money on something that doesn’t work. And be sure that if you have any heart health issues, diabetes, or other chronic disease, that you check with a qualified healthcare provider first before starting any new weight loss support supplement.

Best Types of Supplements for Building Muscle

You know that lifting heavy and eating right is the best way to build muscle. You know that it takes hard work and determination to accomplish this feat.

You’ve also heard that you can add supplements to help you build muscle faster. Maybe your friends have suggested that you take them to help you see faster results.

But do they actually work? Are they worth your hard-earned dollars?

Well, it’s not such a black-and-white answer.

There are some effective supplements out there that can certainly optimize your performance and fill in the gaps in your nutrition. But there are also many more that are utterly and completely useless.

They make some really ridiculous and outlandish claims about how you can pack on 16 pounds of muscle in as little as 12 weeks (no, really, I’m serious).

We’re going to sift through the garbage and really determine what’s worth your hard-earned money to help you reach your goals faster!

Helpful Supplements for Muscle Growth

Whey or Plant Protein Powder

Well, this one’s a no-brainer. We’ve all heard how good high amounts of protein are for us when on our quest to build muscle.

It helps us to repair the muscle after we damaged it in the gym. It prepares our bodies to get ready for the next session in order to begin the process all over again, so that over time, you’re able to build that dream physique you’ve been looking for.

But it’s quite difficult to get the required amount through diet alone to achieve our muscle-building goals. Often times, it’s just not practical.

Also, there are so many different kinds out there. Whey, casein, plant, egg, the list goes on. It can be difficult to choose one over the other.

What varies between them primarily are its rates of digestion. Though they may digest at different speeds, as long as you are reaching your protein targets for the day, it doesn’t matter all too much.

But for the most optimal results and if you’re a regular omnivore (eat both plant and animal products), stick with whey.

If you’re a vegan or vegetarian, or you simply don’t want to consume dairy products, go with a plant-based protein powder such as pea or brown rice. Don’t worry; the package will make it easy enough to point out if it’s whey or plant protein.

That’s why protein supplementation was developed; so that this problem could be solved. This shouldn’t be your primary source of protein. However, this can significantly help you reach those high protein goals.

Much research has shown that the optimal level of protein to consume for building muscle is relative; approximately 1.6 g/kg of body weight (or for us American folks that’s 0.72 g/lb of body weight).

So throwing a scoop or two of this into a shake once per day should be plenty of assistance for reaching your protein target throughout the day.

How Much To Take

25 grams post-workout & on an “as-needed basis” in order to reach your protein goals for the day.

Creatine Monohydrate

I’m sure you’ve heard of this one before. I’m also quite sure you’ve heard some nasty (yet unjustified) things about it, such as: “creatine is a steroid” or “It’s bad for your kidneys” or “It negatively affects your heart”.

Stop it. No. It doesn’t do any of those things nor is it a steroid.

Research has proven time and time again that even those with renal (kidney) issues; creatine has not shown any signs of negative effects on the individual taking a standard dose of 3-5 grams daily.

In fact, in most individuals, many positive effects are seen not only in building muscle and increasing strength, but also as an alternative treatment for ischemic heart disease and neurodegenerative disorders.

Pretty fascinating, don’t you think?

Creatine doesn’t increase muscle mass directly, per se. However, what it does directly affect is one’s performance; more specifically strength and power.

When you increase these variables, then muscle is ought to follow, increasing strength by as much as 13%!

For a dietary supplement, that is extremely significant.

How Much To Take

5 grams pre-workout once per day is usually the recommended amount.

Taking it 30 minutes beforehand will allow it enough time to saturate the muscle.

Commonly, you’ll see that many manufacturers suggest loading 20 grams per day for one week. However, this isn’t really necessary, as you’ll muscles will become saturated with creatine over time as you take it once every day.

I would suggest taking it on non-workout days as it’ll allow your muscles to become saturated more quickly. The time of day you take it doesn’t matter on non-workout days.

Citrulline Malate

You can often find this amino acid in many pre-workout supplements nowadays, but you can also find it as a standalone supplement as well, often in powder form that is unflavored.

What does it do?

Well, it has proven to have the ability of prominently increasing one’s aerobic output (think most types of cardiovascular exercise or high rep sets of strength training). But also, another neat aspect of this supplement is that it commonly reduces soreness the days following intense exercise bouts.

However, the one thing to be careful about here is that many supplement and sports nutrition companies tout that it reduces time to exhaustion. Though true in some anecdotal cases, the research has been unable to thoroughly prove this particular claim, so don’t get your hopes up too high in that regard.

Don’t be discouraged though, this is a fantastic ingredient nonetheless.

The smart thing to do here would be to pair it with creatine in a pre-workout drink that will work as both a recovery enhancer and strength booster!

How Much To Take

6-8 grams pre-workout is plenty once per day on workout days about 30 minutes before your workout.

You don’t have to take it on non-workout days.

Be on the lookout, as many labels put the dosage in milligrams (mg) rather than grams (g), so that would convert to 6,000-8,000 mg.

Beta-Alanine

Beta-Alanine is another amino-acid and works in a very similar way to citrulline malate in that is works best for higher rep sets and aerobic types of training.

A review of many studies (called a meta-analysis in the scientific literature) showed a 2.85% increase in muscular endurance, which is essentially the reps one can perform until exhaustion, for exercise that lasted between 60-240 seconds.

Also, don’t be alarmed if you feel a little tingling when you take this supplement. This is a phenomenon known as paresthesia. This is a harmless sensation you may feel in the face, arms, or legs after ingesting.

Don’t worry, over time, the feeling usually goes away.

How Much To Take

Anywhere between 2-5 grams is plenty before your workouts 30 minutes beforehand. Again, taking it on non-workout days is not necessary.

Caffeine

Oh yes, I bet you’re very familiar with this wonderful compound that’s found in many beverages across the world, including coffees, teas, and sodas. But what makes caffeine so special for building muscle though?

Caffeine is a very effective performance enhancer. Again, like most supplements, it won’t put slabs of muscle directly on your body for you. You have to work for it. However, what caffeine does in particular is make that work much easier to perform.

Being the most popular stimulant taken across the globe, scientists over the years have gotten to conducting experiments on a wide variety of populations to witness how it affects them; most particularly in athletic and fitness realms.

One meta-analysis of 10 different studies illustrated that caffeine was able to increase maximal muscle strength and power significantly compared to placebo groups, particularly during upper body training.

Even more surprising is that one study in particular showed that power output was significantly increased when performing quick bouts of intense activity such as sprints and Olympic weightlifting even when deprived of sleep, getting less than 6 hours per night on a consistent basis!

How Much To Take

Most of the literature has shown that 3-5mg/kg of bodyweight (1.3-2.25g/lb) works just well for most people. Take it 20-30 minutes pre-workout.

WARNING

However, one thing I must address before I continue is that everybody has a different caffeine tolerance. Some people can drink coffee by their bedside and still fall right back asleep, while others take one sip of the stuff and it gives them uncomfortable levels of anxiety.

Taking too much caffeine can lead to nervousness, insomnia, nausea, and anxiety.

Use trial and error if you are not habituated to taking caffeine. Start off with a small dose of 0.5mg/lb and continue from there.

If you continue to see positive results, then continue taking up to the suggested dose. Better safe than sorry. Okay…let’s continue!

Fish Oil

Kind of weird to see a general health supplement on this list, huh?

The reason I put this one on here is because fish oil has many amazing health benefits. We won’t dive into great detail on all of them (because there are a ton!), but what I’ll concentrate on the most here is its anti-inflammatory properties.

When we’re lifting weights, we are breaking down the muscle and literally tearing the fibers (called micro tears). Before the recovery process begins, inflammation takes place, as this is the body’s natural response to this phenomenon. This is what we call acute inflammation. This is normal and healthy. Nothing really to worry about here.

It’s when that inflammation turns chronic (meaning it’s been continuing and not stopping for a period of months and years at a time) is when we begin to run into trouble.

Why is chronic inflammation bad?

Well, let’s think of the elderly for a minute. Why do they experience muscle loss (sarcopenia) over the years as they age? Well, there are many factors that play a role, but a chronic state of inflammation is one of them.

Over years and years of continued inflammation, these individuals begin to lose the ability to synthesize protein properly, thus resulting in a diminished ability to build muscle.

So what does this have to do with us that are younger and are training to keep ourselves healthy and looking good? This inflammation has the same ability to inhibit our muscle-building goals. This is where the fish oil comes in handy.

Fish oil has been proven to be a significant anti-inflammatory agent in both animal and human trials time and time again.

This is very encouraging news, as we are able to keep inflammation at a healthy level that favors building muscle instead of losing it. So it would make perfect sense to take this with whatever general health supplements you may take, such as a multivitamin or what have you.

How Much To Take

Most experts recommend around 2-3 grams of pure DHA and EPA per day.

This does NOT mean total grams of just fish oil alone. This means the DHA and EPA components only, which are those omega 3’s you hear a lot about.

Read the label carefully to make sure you’re getting enough EPA and DHA, or else supplementing with it would be almost useless.

Take it whenever you’d like during the day, as timing doesn’t matter too much with this supplement.

Essential Amino Acid Complex

Wait a second; are you talking about BCAA’s (Branched Chain Amino Acids)? No, I’m not, and here’s why.

The body utilizes many amino acids to go through the process of protein synthesis, which is the metabolic process that helps you to build muscle over time. However, 9 of them your body can’t produce on its own. You either have to get them through your diet or supplementing with them.

The ever-so-popular BCAA supplement contains 3 of the 9 essential amino acids. These 3 amino acids are unique in that they are directly synthesized in the muscle for use as opposed to having to bypass the liver first. Because of this, they play a special role in protein synthesis.

However, the caveat here is that you need all 9 essential amino acids in order to stimulate protein synthesis.

Having an influx of 3 out of the 9 won’t activate protein synthesis nearly as potently than if all optimal levels of the 9 essential amino acids were present. In fact, if you’re body doesn’t have enough of the other 6 amino acids, than it will break down (catabolize) muscle tissue in order to obtain it.

Not something we want, that’s for sure!

Along with this, research has shown us that BCAA’s won’t make us any more apt to build muscle than obtaining enough protein through diet and protein powder supplementation, despite what many of the supplement companies claim they do.

This is where an essential amino acid complex plays a big role. These contain all 9 essential amino acids you need to build muscle optimally.

This is the next best thing to a good quality protein powder. If you can spare a little extra cash, this is a nice add-on to have in your arsenal for when you aren’t in an ideal situation to eat a regular meal or maybe you simply don’t want the thickness of a standard protein shake.

These are often a lot thinner in consistency due to it not containing any of the non-essential amino acids. They are also flavored in a powder form, most often in fruity flavors, to make it much more palatable.

How Much To Take

Although exact doses for each amino acid in isolation hasn’t been established as of yet, the optimal dose for total grams of essential amino acids lies between 10-12 grams, with 2-3 grams coming from leucine, which plays the biggest role in protein synthesis.

I would suggest taking this when you know it may be a while between high-protein meals. This will provide you with a better chance of preventing muscle loss when in a calorie deficit or enhancing muscle growth when looking to gain muscle size.

Weight Gain Powders

This is more of an honorable mention here, as there is not any research currently on these powders in isolation.

In essence, it is the same concept as protein powder, but with added carbohydrates and fats. These are high in calories, ranging from 500-1200 calories. They often contain the same amount of protein as 2 scoops of a standard protein powder (50 grams or so), 100-200 grams of carbohydrates, and up to 15 grams of fat on average.

Basically, it is condensed and preserved calories.

Weight gainers are good for those who really struggle to pack on the pounds due to a lack of appetite, as these are often much less filling than standard meals are. If you aren’t taking in enough calories, you simply won’t build muscle. Plain and simple.

The one thing to watch out for here is that many of them use fillers and other cheap ingredients that have you feeling less than optimal, especially during training. This is usually because of poor quality carbohydrates such as maltodextrin and dextrose being used as a majority of the carbohydrates, which are types of fast-digesting sugars.

Look for weight gainers that contain healthier sources of carbs such as oat bran and buckwheat as the primary sources of carbohydrates. You’ll know that they are the primary sources when they are listed earlier in the ingredients list compared to the sugars and other fillers.

How Much To Take

On an as-needed basis, depending on how many calories you are obtaining through food already. If you tend to live a busier lifestyle where it is more difficult to fit in regular meals, then this should be more of a staple in your supplementation regime.

Wrapping Up

Well, there you have it!

supplements that are most definitely worth your investment if you’re looking to optimize those muscle-building goals and augment that hard work you put in the gym each and every day.

These certainly won’t replace a proper diet and exercise regimen, but they can most certainly aid you in the process.