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NZT-48 claims to be the ultimate brain booster, but let’s take a closer look at the research to see if it lives up to its promises.
Problems with NZT-48
One major concern with supplements like NZT-48 is the lack of solid evidence supporting their claimed benefits. Many of these supplements rely on studies conducted on cells and animals, which offer valuable insights but are not sufficient proof of benefits in humans. To establish safety and efficacy, human clinical trials are essential. These trials provide direct evidence of real benefits and potential risks.
Moreover, the research on cognitive supplements often focuses on individuals with cognitive problems like Alzheimer’s or dementia, not healthy individuals. Just like antibiotics treat bacterial infections in sick individuals, cognitive supplements may be better at addressing deficits rather than enhancing brain function in generally healthy individuals.
Ingredients
Another issue with supplements like NZT-48 is the dilution effect. With numerous ingredients crammed into the formula, the amount of each ingredient per capsule is often quite small. In the case of NZT-48, each capsule contains a total of 750 mg with 23 listed ingredients. This averages out to a mere 32 mg per ingredient, which may not be enough to produce noticeable effects. Quantity matters in supplements, and inadequate doses can lead to suboptimal results. It’s important to determine the recommended level of each ingredient through research and human trials to ensure effectiveness.
As we examine the ingredients in NZT-48, these common problems consistently emerge, casting doubts on its true efficacy.
Alpha GPC
Alpha GPC is a type of choline, an important nutrient found naturally in certain foods like eggs.
While there is evidence that Alpha GPC may improve cognitive function in individuals with Alzheimer’s disease, the positive effects were observed at high doses of 1200 mg per day for up to 6 months. It’s important to note that NZT-48 does not provide such doses, and the studies focused specifically on Alzheimer’s patients, not healthy adults.
The idea that Alpha GPC can enhance cognition in healthy adults is based on the belief that it acts as a precursor to acetylcholine, a neurotransmitter. Supporters suggest that regular use of Alpha GPC could raise acetylcholine levels in the brain, potentially benefiting cognitive functions. However, this notion lacks support from human trials, and there is no scientific evidence to back up this claim for individuals without Alzheimer’s.
In fact, long-term use of Alpha GPC supplements has been associated with an increased risk of stroke. Unless you have a specific medical reason, such as Alzheimer’s disease, it’s advisable to avoid taking Alpha GPC.
EGCG
EGCG, which can be found in green tea and its extracts, may provide a slight improvement in cognitive function when combined with caffeine. However, there are some studies that show no clear benefits. To see modest improvements, it is recommended to take doses of around 100-200 mg, which is equivalent to roughly 1-2 cups of green tea.
Caffeine and Guarana
Caffeine and guarana, which is essentially another source of caffeine, are well-known for boosting mental alertness and enhancing cognitive performance. The cognitive effects of NZT-48 are likely attributed to the caffeine it contains. However, the exact amount of caffeine in NZT-48 is not specified, making it potentially riskier to use, especially for those who are sensitive to the potential side effects of caffeine.
5-HTP, Ashwagandha, and Rhodiola
While 5-HTP, Ashwagandha, and Rhodiola have shown benefits in improving mood, such as managing stress, depression, or anxiety, there is no evidence suggesting that they can enhance cognition in humans. Additionally, the doses used in studies are typically much higher than what NZT-48 likely contains.
Theobromine
Theobromine, which is found in dark chocolate and cocoa extracts, has conflicting research regarding its impact on cognitive function in healthy adults. In older adults, cocoa does not seem to boost cognition. In younger adults, it shows some improvement in certain cognitive measures, but the effective doses in these studies were significantly higher than what NZT-48 is likely to provide.
Benfotiamine and B vitamins
Benfotiamine, a fat-soluble form of vitamin B1, along with B vitamins like B6, B12, and folic acid, play important roles in brain health. However, studies consistently show that supplementing with these vitamins does not noticeably affect cognitive function. The belief that vitamin B12 enhances cognitive function has been debunked by research, which found no cognitive improvement in healthy adults with B12 supplementation.
Phenylalanine
Phenylalanine, an amino acid, has been studied for its potential cognitive benefits in ADHD. However, research suggests that it does not provide any advantages over a placebo.
Acetyl-L-Carnitine
Research indicates that taking Acetyl-L-Carnitine may improve certain aspects of cognitive function and memory in older individuals who are experiencing age-related cognitive decline. However, the positive effects were observed at doses of 1500-2000 mg per day for a period of 3 months, specifically in elderly patients with cognitive deficits, not in healthy adults.
N-acetyl-L-Tyrosine and L-Theanine
N-Acetyl-L-Tyrosine, a more soluble form of L-tyrosine, and L-theanine are amino acids that show potential for improving cognitive function, especially in individuals facing stress or anxiety. They are often combined with caffeine, although it’s unclear if adding L-theanine enhances cognitive performance beyond caffeine alone. The effective doses, particularly for tyrosine, are quite high and likely exceed what NZT-48 provides.
Gingko biloba
Gingko biloba is often studied for its potential to enhance cognition in patients with conditions like dementia. It has also shown potential benefits for cognitive function in healthy adults. However, the doses studied range from 240-360 mg, which likely exceeds what NZT-48 provides. Additionally, these studies often use specialized or standardized extracts like GK501 or EGb 761, while NZT-48 relies on generic ginkgo extracts.
Bacopaside
Bacopaside is a compound derived from the herb Bacopa monnieri. Some evidence suggests it could improve certain cognitive measures in healthy adults, although the data is conflicting. However, the doses studied in healthy adults are in the hundreds of milligrams per day, likely exceeding what NZT-48 provides.
NADH
NADH is a coenzyme involved in various bodily reactions, but there is no human trial evidence supporting its use to enhance cognitive function in healthy adults.
Phosphatidylserine
Phosphatidylserine is an important building block for nerve cells and shows promise in addressing age-related cognitive decline. Studies with individuals experiencing cognitive decline indicate that taking 100 mg of phosphatidylserine three times daily for up to 6 months may improve various cognitive functions. However, the cognitive benefits of phosphatidylserine for healthy individuals are still uncertain.
Uridine-5 Monophosphate
Uridine-5 Monophosphate is one of several nucleotide supplements with mainly theoretical evidence for health benefits, but there is a lack of solid human trials.
Mucuna pruriens
Also known as Cowhage, Mucuna pruriens is a traditional Ayurvedic herb with weak evidence supporting its use in Parkinson’s disease due to its high L-DOPA content. However, there is no evidence suggesting its usefulness for cognition.
Rauwolscine
Rauwolscine has not demonstrated any evidence of being helpful for cognitive function. Moreover, it may not be safe to use, and Health Canada has banned it as a supplement ingredient.
Huperzine A
Huperzine A is a compound derived from plants like Chinese club moss. It works by blocking an enzyme called acetylcholinesterase, which breaks down acetylcholine in the brain. By inhibiting this enzyme, Huperzine A increases the levels of acetylcholine, which can improve communication between brain cells and potentially enhance cognitive processes.
In the context of Alzheimer’s disease, Huperzine A has shown promise in improving memory, cognitive function, and behavior. It is commonly used in China for treating this condition. However, for healthy adults without Alzheimer’s disease, Huperzine A is unlikely to have a significant impact on cognitive function. The benefits of using acetylcholinesterase inhibitors like Huperzine A seem to be more relevant for individuals with Alzheimer’s disease rather than those without the condition.
Ingredient analysis summary
Let’s summarize our ingredient analysis for NZT-48.
First, we removed ingredients without scientific evidence supporting cognitive improvement, as they seem to be filler ingredients.
- Eliminated: NAHD, Uridine-5 Monophosphate, Rauwolscine
Next, we excluded ingredients that, despite some research, haven’t shown any real benefits beyond a placebo effect.
- Eliminated: Benfotiamine and B vitamins, Phenylalanine.
We then identified ingredients that may have mood-related benefits but are unlikely to directly boost cognitive performance.
- Eliminated: 5-HTP, Ashwagandha, Rhodiola.
Moving on, we recognized ingredients that have shown potential benefits for cognitive performance but mainly in individuals with cognitive issues like dementia. They may not be as useful for healthy individuals.
- Eliminated: Alpha GPC, Acetyl-L-Carnitine, Phosphatidylserine, Mucuna pruriens, Huperzine A.
Now, let’s focus on ingredients that have shown possible cognitive benefits specifically for healthy individuals and evaluate the strength of the evidence.
- Eliminated: EGCG, Caffeine, Guarana, Theobromine, N-acetyl-L-Tyrosine, Gingko biloba, Bacopaside, Theanine.
Finally, we eliminated ingredients with doses that are likely too low to provide any noticeable benefit.
- Potential: Caffeine and guarana, EGCG or green tea extracts, Huperzine A.
Among these, only caffeine and EGCG have shown benefits for healthy adults. The remaining ingredients either don’t improve cognitive function in healthy individuals or have doses that are too low to be effective.
Is NZT-48 Effective?
NZT-48 effective for boosting brain function? Let’s evaluate its effectiveness and see if it lives up to its claims. In my opinion, NZT-48 is comparable to having a couple of cups of coffee or green tea. For healthy individuals, it’s unlikely to be significantly more effective than combining caffeine with a green tea extract. However, if you’re dealing with Alzheimer’s disease, the inclusion of Huperzine A in NZT-48 might offer some potential benefits.
The main issue with NZT-48 doesn’t lie in the choice of ingredients. Many of the ingredients are actually beneficial for a brain-boosting supplement, and there is scientific evidence supporting their use. The real problem arises from the fact that NZT-48 has tried to include almost every possible ingredient in one pill. This approach makes it difficult to provide sufficient therapeutic doses of most ingredients. As a result, the supplement can only deliver therapeutic doses of caffeine, Huperzine A, and possibly EGCG.
Overall rating
Rating NZT-48 by effectiveness for improving cognition, I’m giving it a C. It’ll functionally be about as good as drinking a cup of coffee or green tea.
Rating it by cost, I’m giving it a D. It can be easily replicated at a much cheaper cost by getting the generic ingredients individually.
Rating it for safety, I’m giving it a D. There are a number of ingredients that have the potential to interfere with medications, and because they mix in so many of them, it’s hard to fully untangle all the possible side effects.
Overall rating, I’m giving a D. I would not recommend it at all.
Top alternatives to NZT-48
If you’re looking to achieve effects similar to, or perhaps even better than, those of NZT-48, I would combine a quality:
- Caffeine anhydrous – 1 cap / day
- Green tea (caps) – 2 to 4 caps / day
- Green tea (teabags, decaf) – 1 to 4 cups / day
- Green tea (teabags) – 1 to 4 cups / day
- Huperzine A – 1 to 2 caps / day
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Citations
Baker LD, Manson JE, Rapp SR, et al. Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial. Alzheimers Dement. 2023;19(4):1308-1319. doi:10.1002/alz.12767
Cilia R, Laguna J, Cassani E, et al. Mucuna pruriens in Parkinson disease: A double-blind, randomized, controlled, crossover study. Neurology. 2017;89(5):432-438. doi:10.1212/WNL.0000000000004175
De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer’s dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther. 2003;25(1):178-193. doi:10.1016/s0149-2918(03)90023-3
Decroix L, van Schuerbeek P, Tonoli C, et al. The effect of acute cocoa flavanol intake on the BOLD response and cognitive function in type 1 diabetes: a randomized, placebo-controlled, double-blinded cross-over pilot study. Psychopharmacology (Berl). 2019;236(12):3421-3428. doi:10.1007/s00213-019-05306-z
Devita M, Masina F, Mapelli D, Anselmi P, Sergi G, Coin A. Acetylcholinesterase inhibitors and cognitive stimulation, combined and alone, in treating individuals with mild Alzheimer’s disease. Aging Clin Exp Res. 2021;33(11):3039-3045. doi:10.1007/s40520-021-01837-8
Einöther SJ, Martens VE, Rycroft JA, De Bruin EA. L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness. Appetite. 2010;54(2):406-409. doi:10.1016/j.appet.2010.01.003
Foxe JJ, Morie KP, Laud PJ, Rowson MJ, de Bruin EA, Kelly SP. Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task. Neuropharmacology. 2012;62(7):2320-2327. doi:10.1016/j.neuropharm.2012.01.020
Hoffer LJ, Sher K, Saboohi F, Bernier P, MacNamara EM, Rinzler D. N-acetyl-L-tyrosine as a tyrosine source in adult parenteral nutrition. JPEN J Parenter Enteral Nutr. 2003;27(6):419-422. doi:10.1177/0148607103027006419
Javelle F, Lampit A, Bloch W, Häussermann P, Johnson SL, Zimmer P. Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis. Nutr Rev. 2020;78(1):77-88. doi:10.1093/nutrit/nuz039
Jówko E. Green Tea Catechins and Sport Performance. In: Lamprecht M, ed. Antioxidants in Sport Nutrition. Boca Raton (FL): CRC Press/Taylor & Francis; 2015.
Katzenschlager R, Evans A, Manson A, et al. Mucuna pruriens in Parkinson’s disease: a double blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry. 2004;75(12):1672-1677. doi:10.1136/jnnp.2003.028761
Kennedy DO, Scholey AB, Wesnes KA. The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. Psychopharmacology (Berl). 2000;151(4):416-423. doi:10.1007/s002130000501
Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, Limpeanchob N, Norman Scholfield C. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-535. doi:10.1016/j.jep.2013.11.008
Lee G, Choi S, Chang J, et al. Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years. JAMA Netw Open. 2021;4(11):e2136008. Published 2021 Nov 1. doi:10.1001/jamanetworkopen.2021.36008
Mastroiacovo D, Kwik-Uribe C, Grassi D, et al. Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) Study–a randomized controlled trial. Am J Clin Nutr. 2015;101(3):538-548. doi:10.3945/ajcn.114.092189
McPhee GM, Downey LA, Wesnes KA, Stough C. The Neurocognitive Effects of Bacopa monnieri and Cognitive Training on Markers of Brain Microstructure in Healthy Older Adults. Front Aging Neurosci. 2021;13:638109. Published 2021 Feb 22. doi:10.3389/fnagi.2021.638109
Moreta MP, Burgos-Alonso N, Torrecilla M, Marco-Contelles J, Bruzos-Cidón C. Efficacy of Acetylcholinesterase Inhibitors on Cognitive Function in Alzheimer’s Disease. Review of Reviews. Biomedicines. 2021;9(11):1689. Published 2021 Nov 15. doi:10.3390/biomedicines9111689
Passeri M, Cucinotta D, Bonati PA, Iannuccelli M, Parnetti L, Senin U. Acetyl-L-carnitine in the treatment of mildly demented elderly patients. Int J Clin Pharmacol Res. 1990;10(1-2):75-79.
Roodenrys S, Booth D, Bulzomi S, Phipps A, Micallef C, Smoker J. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology. 2002;27(2):279-281. doi:10.1016/S0893-133X(01)00419-5
Sagaro GG, Traini E, Amenta F. Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2023;92(1):59-70. doi:10.3233/JAD-221189
Scholey AB, French SJ, Morris PJ, Kennedy DO, Milne AL, Haskell CF. Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort. J Psychopharmacol. 2010;24(10):1505-1514. doi:10.1177/0269881109106923
Stough C, Lloyd J, Clarke J, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects [published correction appears in Psychopharmacology (Berl). 2015 Jul;232(13):2427. Dosage error in article text]. Psychopharmacology (Berl). 2001;156(4):481-484. doi:10.1007/s002130100815
Wessinger CM, Inman CL, Weinstock J, Weiss EP. Effect of Huperzine A on Cognitive Function and Perception of Effort during Exercise: A Randomized Double-Blind Crossover Trial. Int J Exerc Sci. 2021 Aug 1;14(2):727-741. PMID: 34567353; PMCID: PMC8439683.
Wightman EL, Haskell CF, Forster JS, Veasey RC, Kennedy DO. Epigallocatechin gallate, cerebral blood flow parameters, cognitive performance and mood in healthy humans: a double-blind, placebo-controlled, crossover investigation. Hum Psychopharmacol. 2012;27(2):177-186. doi:10.1002/hup.1263
Yang G, Wang Y, Tian J, Liu JP. Huperzine A for Alzheimer’s disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One. 2013;8(9):e74916. Published 2013 Sep 23. doi:10.1371/journal.pone.0074916
Yesavage JA, Friedman L, Ashford JW, et al. Acetylcholinesterase inhibitor in combination with cognitive training in older adults. J Gerontol B Psychol Sci Soc Sci. 2008;63(5):P288-P294. doi:10.1093/geronb/63.5.p288
Zametkin AJ, Karoum F, Rapoport JL. Treatment of hyperactive children with D-phenylalanine. Am J Psychiatry. 1987;144(6):792-794. doi:10.1176/ajp.144.6.792
See also
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