Peptides for Energy and Fatigue: What Is Prescribed and What to Rule Out

"Low energy" suggests a reservoir that has run down. The biology is closer to an assembly line. Glucose and fatty acids are broken down in the cytoplasm and the mitochondrial matrix, and their electrons are handed to carrier molecules, which deliver them to the electron transport chain embedded in the folded inner mitochondrial membrane. The chain pumps protons across that membrane, and their return drives ATP synthase, which makes the ATP every muscle contraction and nerve impulse spends.

Each step has inputs: the carnitine shuttle for fatty acids, NAD+ to carry electrons, cardiolipin to hold the transport chain in shape, iron, B12 and folate for the red cells that deliver oxygen, thyroid hormone to set the throughput. Remove any one and the line slows.

Sort the compounds on this page by the step they touch. Methylcobalamin and L-carnitine are substrate and transport problems: they matter when the body is short of them and do little when it is not. NAD+ is a cofactor problem: the carrier the whole process depends on, which human tissue studies report declining with age (PLOS ONE, 2012). SS-31 is a membrane problem: it binds cardiolipin. MOTS-c is a signaling problem: a peptide encoded by the mitochondrion itself that tells the cell how to handle metabolic stress. Glutathione is the cleanup crew for the reactive oxygen species the chain leaks. A person whose fatigue is an iron problem gets nothing from a cofactor, and a person whose fatigue is a sleep problem gets nothing from any of them.

Persistent tiredness is one of the most common reasons adults see a physician, and in most visits the cause is found in the history or on a routine panel. Chronic fatigue syndrome, defined by the 1994 criteria in the Annals of Internal Medicine, is a small minority of the people searching for "peptides for energy". Most are somewhere more mundane, and the mundane causes have treatments that work better than anything here.

Nicotinamide adenine dinucleotide is a coenzyme, not a peptide. It sits in every cell you have, and its job is to carry electrons: in glycolysis and the citric acid cycle it picks them up from broken-down nutrients, becoming NADH, then hands them to the electron transport chain, where their energy makes ATP. Sirtuins and PARP enzymes, which handle DNA repair and the stress response, consume NAD+ rather than recycling it. A 2012 PLOS ONE study reported lower NAD+ and more oxidative stress in older human tissue; reviews in Science (2015) and Cell Metabolism (2018) set out the case that this decline is part of aging.

The human data needs careful reading, because almost all of it uses oral precursors rather than NAD+ itself. Nicotinamide riboside by mouth raised blood NAD+ in healthy volunteers (PLoS One, 2017), in healthy middle-aged and older adults (Nature Communications, 2018) and in healthy overweight adults with no safety signal (Scientific Reports, 2019), but did not improve insulin sensitivity in obese men (American Journal of Clinical Nutrition, 2018). Nicotinamide mononucleotide improved muscle insulin sensitivity in prediabetic postmenopausal women (Science, 2021) and raised NAD+ and walking distance in healthy middle-aged adults (GeroScience, 2023). Nicotinamide riboside raised brain NAD+ in Parkinson's disease (Cell Metabolism, 2022) and gave a modest walking benefit in peripheral artery disease (Nature Communications, 2024).

For NAD+ given directly, the data is thin. A 2019 pilot in Frontiers in Aging Neuroscience infused it over six hours and found plasma NAD+ did not rise for roughly two hours while metabolites appeared in urine. For fatigue, the trials that exist used oral NADH, the reduced form: a small 1999 crossover in Annals of Allergy, Asthma and Immunology, and two trials of NADH with coenzyme Q10 (Clinical Nutrition, 2016; Nutrients, 2021) reporting reduced fatigue perception in chronic fatigue syndrome. There are no randomized human trials of subcutaneous NAD+ for fatigue.

Who it suits: the person whose workup is genuinely clear, who describes flat afternoons rather than sleepiness, and who understands that the mechanism is well described while the evidence for this route is not. NAD+ Injection is the full-strength vial.

NAD+ 500 mg is the same molecule at half the concentration, which some physicians choose for a first month so any flushing or nausea can be judged at a lower exposure. It is not a different treatment.

The NAD+ Nasal Spray exists for the person who will not inject. Reviews in the Journal of Controlled Release (2003) and Advanced Drug Delivery Reviews (2012) describe nasal delivery, and rat studies in Frontiers in Bioscience (2007) and the Journal of Neurotrauma (2012) report intranasal NAD+ reaching the brain after stroke and head trauma. Those are rodent studies of acute injury, not human fatigue trials. The spray carries a lower total dose per bottle, and no trial has compared the routes.

MOTS-c is a peptide encoded in mitochondrial DNA rather than in the nucleus, which is most of why it drew attention; mitochondria carry their own small genome, and MOTS-c is one of the few proteins written there. The 2015 Cell Metabolism paper that named it reported that in mice it activated AMPK, the cell's low-energy sensor, and prevented diet-induced obesity and insulin resistance; a 2018 follow-up described it moving into the nucleus under metabolic stress.

The human work is observational. A 2021 Nature Communications paper reported that exercise raises MOTS-c in the plasma and muscle of young men, and that treating aged mice improved their physical capacity. Plasma MOTS-c has been reported lower in diabetes (Frontiers in Endocrinology, 2019), associated with insulin sensitivity in lean adults (Journal of Investigative Medicine, 2018) and with obesity (Archives of Endocrinology and Metabolism, 2025), and a mitochondrial DNA variant altering the peptide has been linked to type 2 diabetes (Aging, 2021). That describes MOTS-c as a marker and a mechanism. There are no randomized human trials of MOTS-c.

Who it suits: the person whose fatigue travels with weight gain or insulin resistance, where the AMPK mechanism is aimed at the right problem. MOTS-c is the single-agent vial. Tested athletes should read the anti-doping section first.

SS-31, also called elamipretide, is a four-amino-acid peptide designed to concentrate in the inner mitochondrial membrane, where it binds cardiolipin, the phospholipid that holds the electron transport chain in efficient arrangement and whose damage is a recognized feature of mitochondrial dysfunction. A 2014 review in the British Journal of Pharmacology describes it as the first compound built to protect cardiolipin, and a 2013 study in the Journal of the American Society of Nephrology reported it restoring ATP production in ischemic rat kidney mitochondria.

SS-31 is the one compound here with a genuine trial program. In primary mitochondrial myopathy, a group of rare genetic diseases, a 2018 dose-escalation study in Neurology reported better six-minute walk distance at the highest dose; a 2020 crossover in the Journal of Cachexia, Sarcopenia and Muscle found no significant change in walking but a signal on patient-reported fatigue; and MMPOWER-3 (Neurology, 2023), 218 patients over 24 weeks, did not meet its primary endpoints, with a 2024 post hoc analysis in the Orphanet Journal of Rare Diseases suggesting the response differed by genotype. In Barth syndrome, a cardiolipin disorder, the TAZPOWER crossover (Genetics in Medicine, 2021) missed its primary endpoints but its open-label extension reported improvements sustained through 168 weeks (Genetics in Medicine, 2024), and that data underpinned the FDA's 2025 accelerated approval of elamipretide (Drug Discovery and Therapeutics, 2026). Phase 2 trials in heart failure (Journal of Cardiac Failure, 2020) and macular degeneration (Ophthalmology Science, 2024) are also published.

So: real randomized trials, in rare genetic mitochondrial diseases, with mixed results and one approval. There are no randomized human trials of SS-31 in people with fatigue who do not have a mitochondrial disease.

Who it suits: the person whose physician has reason to think mitochondrial function itself is limiting, after the ordinary causes are gone. SS-31 is supplied as a vial.

Methylcobalamin is the active coenzyme form of vitamin B12, and the least glamorous thing here. It is the cofactor for methionine synthase in the methylation cycle and is required for myelin maintenance and red blood cell formation. Deficiency is common and under-recognized (New England Journal of Medicine, 2013; Nature Reviews Disease Primers, 2017), presents with fatigue, numbness and low mood long before anemia, and is more frequent with long-term metformin (Journal of Clinical Endocrinology and Metabolism, 2016) and plant-based diets (Nutrition Reviews, 2013).

In genuine deficiency, replacement changes how people feel. What the evidence does not support is B12 as a general energy shot. High-dose oral cobalamin corrects deficiency as well as injections (Blood, 1998; Cochrane, 2018), and a 2015 paper in Molecular Nutrition and Food Research found no evidence the methyl form outperforms other forms. A 2018 randomized trial in Clinical Nutrition ESPEN gave surplus B12 to people with bowel disease and reported no reduction in fatigue. At a normal B12 level it does very little, and honest prescribers say so.

Who it suits: the person with a low or borderline serum B12, malabsorption, long-term metformin use, or a plant-based diet. Methylcobalamin is the single-agent injection; the B12 in Lipo-B is combined with lipotropic agents and belongs to a body-composition conversation.

L-carnitine is a quaternary ammonium compound synthesized from lysine and methionine, again not a peptide. It runs the carnitine shuttle: the mechanism that carries long-chain fatty acids across the inner mitochondrial membrane so they can be burned. That step is rate-limiting for fat oxidation, which is why it appears in both fatigue and body-composition conversations. Work in the Journal of Physiology (2007, 2011) showed that raising muscle carnitine in humans over 24 weeks shifted fuel use during exercise.

Human fatigue data exists in specific populations: centenarians given L-carnitine for six months reported less physical and mental fatigue against placebo (American Journal of Clinical Nutrition, 2007), and hemodialysis patients, who are routinely depleted, reported less fatigue after intravenous doses (American Journal of Kidney Diseases, 2001). Meta-analyses of weight trials (Obesity Reviews, 2016; Pharmacological Research, 2020) report a modest effect. Clinical benefit in people who are not deficient is modest, and a 2013 Nature Medicine paper on gut-bacterial conversion of carnitine to TMAO is why a physician asks about cardiovascular history first.

Who it suits: the person training hard whose fatigue is exercise-related, or whose diet plausibly runs carnitine low. L-Carnitine is supplied as a vial.

Glutathione is a tripeptide of glutamate, cysteine and glycine, and the main antioxidant inside your cells (Biochimica et Biophysica Acta, 2013). The biochemistry is solid; evidence that supplementing it produces clinical outcomes is weaker.

Route matters more for glutathione than for anything else here. A 1992 study in the European Journal of Clinical Pharmacology found essentially no rise in plasma glutathione after oral doses, which is why injectable forms exist; later oral trials (European Journal of Nutrition, 2015) reported raised body stores over months. The most relevant trial did not use glutathione itself: a 2023 randomized trial in the Journals of Gerontology gave older adults glycine and N-acetylcysteine, its building blocks, and reported improved glutathione levels, mitochondrial markers and physical function. There are no randomized human trials of injectable glutathione for fatigue.

Who it suits: the person whose physician is treating oxidative load or liver function alongside fatigue, rather than fatigue alone. Glutathione is supplied as a vial.

NAD+ biochemistry is textbook material. Whether administering it raises intracellular NAD+ meaningfully in humans, and whether that changes how a person feels, is where the evidence thins and where marketing most outruns the data.

MOTS-c is preclinical. An association between exercise and plasma MOTS-c is not evidence that injecting MOTS-c reproduces exercise.

SS-31 has been through clinical trials in primary mitochondrial myopathy with mixed results, and use for ordinary fatigue extrapolates from that.

Methylcobalamin and L-carnitine are established in deficiency and modest outside it. Glutathione's injectable fatigue data is absent. None of it establishes an effect size for fatigue in otherwise healthy adults, a human timeline, or superiority of one NAD+ route over another. None of these compounded products is FDA approved. They are made by licensed US pharmacies against a valid prescription, which are peptides FDA approved explains in full. Anyone with a personal history of cancer should raise it, since NAD metabolism intersects with cell proliferation pathways.

A pharmacy compounding under section 503A may use a bulk drug substance if it has a USP or NF monograph, is a component of an FDA-approved drug, or appears on the FDA's 503A bulks list. That list, in 21 CFR 216.23, currently contains six substances, none on this page. For nominated substances not yet decided, the FDA runs an interim policy with three categories: Category 1 under evaluation, Category 2 flagged for significant safety concerns, Category 3 nominated without adequate support.

In the FDA's categories document updated May 14, 2026, nicotinamide adenine dinucleotide (NAD), its reduced form NADH, glutathione, methylcobalamin and acetyl-L-carnitine all sit in Category 1. One specific salt, beta-nicotinamide adenine dinucleotide disodium salt trihydrate, was nominated separately and appears in Category 3. None of the four is in Category 2.

Levocarnitine is also the active ingredient of FDA-approved oral tablets and solutions, so L-carnitine qualifies as a component of an approved drug. There is no FDA-approved methylcobalamin product; the approved injectable B12 is cyanocobalamin. In every case the compounded injection is prepared to your prescription and is not an FDA-approved finished product.

MOTS-c is the one compound here whose status has moved this year. It was previously placed in Category 2. As of the FDA's May 14, 2026 update it appears in none of the three categories, and the FDA's page on substances that may present significant safety risks lists MOTS-c under substances previously in Category 2 whose nominations were withdrawn by the nominators. Separately, on July 23, 2026 the FDA's Pharmacy Compounding Advisory Committee discussed MOTS-c, alongside BPC-157, KPV and TB-500, as a candidate for the 503A bulks list, with obesity and osteoporosis as the uses reviewed. The committee recommends; the FDA's own determination follows and has not been issued.

Elamipretide is now the active ingredient of an FDA-approved drug. Forzinity (NDA 215244) was approved on September 19, 2025 under accelerated approval, to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg, on an intermediate endpoint, with continued approval contingent on a confirmatory trial. Compounded SS-31 is not Forzinity, is not approved for anything, and is not prescribed here for Barth syndrome; whether a compounded preparation is appropriate for a given patient is a decision for the physician and the pharmacy.

The 2026 WADA Prohibited List names MOTS-c explicitly under S4.4.1, as an activator of AMP-activated protein kinase, in the class of hormone and metabolic modulators prohibited at all times. NAD+, elamipretide, L-carnitine, vitamin B12 and glutathione are not named on the 2026 list. A tested athlete should confirm with their governing body and tell their physician before anything is prescribed.

If the night is short, fragmented or unrefreshing, no cofactor fixes a sleep problem. Snoring and witnessed pauses are a sleep-study question; where the issue is falling and staying asleep, DSIP or the SERENITY blend belong to that conversation.

Where fatigue arrives with weight gain or a rising HbA1c, the metabolic problem is upstream of the mitochondria. MOTS-c is aimed at that biology, but the compounds with large randomized trials for weight and glucose are semaglutide and tirzepatide, and a physician will usually want that conversation first.

Fatigue is one of the most common presentations of depression, and it does not respond to an energy product. Where the picture is anxiety and tension rather than energy, Selank is the product aimed at that, and the physician decides whether it belongs in the plan.

Low thyroid output and low testosterone both present as tiredness and both have their own treatments; low testosterone in men is covered in peptides for men over 40. Tiredness while recovering from an illness, surgery or a hard training block is the body allocating resources to repair; where recovery itself is the concern, that is the conversation products such as BPC-157 sit in.

Your physician will tell you if none of the energy products is the right tool. A consultation does not guarantee a prescription, and being declined is refunded.