Categories
Cognitive Health Nootropics

Can We Really Increase Our Intelligence?

According to the psychological literature available, there are two general prospects of intelligence: the uniform one, evaluated in school, which basically addresses linguistic & logical-mathematical intelligence; and the Pluralistic View of Mind, proposed by Howard Gardner in his acclaimed theory of Multiple Intelligences. Two different theories that demand two very different -and eventually opposed- answers to the inquiry of intelligence enhancement.

Intelligence Quotient (IQ) is a certain type of measurement of intellectual ability that came in due to devotion to universal formal education. Thus, IQ tests have been shown to be moderately correlated with grades in elementary, primary, and high school; job performance; professional status; and number of years in school[1]. In this way, the prevalence of IQ tests imply a certain Hereditarian Theory of Intelligence that is rather invariable and stable across time among healthy individuals. According to this approach, intelligence is a unitary entity, an abstraction of an all-purpose system that permeates uniformly in all intellectual activity. Therefore, according to this prospect, the primary basis of intelligence is primarily genetically determined.

Indisputably, IQ tests are limited in some of its applications and have interpretation problems. They do not appropriately assess the role of motivation (it is likely that motivated individuals put more effort in IQ tests and hence score higher), creativity, social skills, practical intelligence, or wisdom, just for mentioning some relevant variables. Nevertheless, Charles Spearman has demonstrated[2], interestingly, that the various subsets that conform the IQ inventory are positively correlated, labeled as the factor G to stand for the general factor that underlies all intellectual ability. This generic problem solving system is what is popularly called “fluid intelligence”, an empirical argument that  rather supports a hereditarian or genetic theory of intelligence.

Indeed, available data from twins research suggest that genes are a primary determinant of this view of intelligence[3]. Thus, there is an important group of psychologists and brain & mind scientists who do not think that it is possible to modify your factor G, even though it is not completely clear how this factor and the environment interact with each other[4]. For instance, Jack Naglieri, an intelligence expert from University of Virginia, prevents us to not confuse ability with knowledge. The right way of measuring intelligence, he argues, is to quantify those abilities that underlie the acquisition of knowledge, independently from the knowledge itself. Thus, this psychologist is implying that intelligence is something relatively independent of the learning experience.

Nonetheless, a renowned article published in the journal Nature by Price and her colleagues challenged this immutable view of intelligence[5]. The study had 33 adolescents, who were 12 to 16-years-old when the study initiated. Price and her team gave them IQ tests, tracked them for four years, and then tested them again with the same measurement tools. The fluctuations in IQ were outstanding: not about a couple points, but 20-plus IQ points. These changes in IQ scores, according to the researchers, were not random — they tracked elegantly with structural and functional brain imaging. Thus, there is also an important group of scientists that maintain that many of the changes in IQ are correlated to changes in the environment, particularly schooling.

It’s analogous to fitness. A teenager who is athletically fit at 14 could be less fit at 18 if they stopped exercising. Conversely, an unfit teenager can become much fitter with exercise.

Furthermore, there is also a certain number of studies that have shown brain changes after several kinds of educational regimens. The study about Tokyo taxi drivers is a especially distinguished one[6]. Scientists conducted memory, visual and spatial information tests and took brain scans using MRI of 79 male trainee Tokyo taxi drivers at the beginning of their training regimen. At the beginning of the study, no variance was found in their brain structure or memory. Three to four years later, however, scientists found a considerable increase in grey matter in the posterior hippocampi, among the 39 trains who performed as taxi drivers. Naturally, this change was not observed in the non-taxi drivers. Thus, this kind of studies suggest that the brain can change to accommodate new knowledge, so future programs for lifelong learning are possible[7].

To sum up, it is not fully clear What intelligence is[8], and hence How to directly increase it.[9] Nonetheless, we can consider intelligence, for practical purposes, as a starting point in life. Naturally, we are born with certain capacities and particular features, but it is later in life when we discover and develop them, regardless of our individual  genetic background. Thus, instead of frustratingly trying to increase your “G” factor (since we do not have a general consensus and determinant scientific evidence yet), what you can do is focus in your multiple crystallized intelligences: the ability to use skills, knowledge, and experience. If you are a scientist, observe and analyze information; if you are a philosopher, organize it and turn it into knowledge; if you are an artist, interpret it. Different areas of intelligence have different weights of importance in each person’s occupational life, and you can definitely get better at specific activities through practice and discipline.

References   [ + ]

1, 8. Intelligence and Achievement: Just how Correlated are they?
2, 9. Summary of Psychology topic Intelligence g Factor
3. McGue , M. Bouchard , T. J. , Jr Iacono , W. G. Lykken , D. T. (1993). Behavioral genetics of cognitive ability: A life-span perspective. In R. Plomin G. E. McClearn (Eds.), Nature, nurture, and psychology (pp. 59-76). Washington, DC: American Psychological Association
4. Nature-nurture and intelligence.
5. Brain scans support findings that IQ can rise or fall significantly during adolescence
6. The Use of Geospatial Information and Spatial Cognition of Taxi Drivers in Tokyo
7. Nurture net of nature: Re-evaluating the role of shared environments in academic achievement and verbal intelligence
Categories
Methylene Blue Nootropics Reviews

Methylene Blue as a Nootropic? (Review)

Since its initial synthesis in 1886, the phenothiazine derivative methylene blue (MB) has been established as a highly versatile chemical agent with a diverse span of uses, ranging from treating malaria to dying textiles[1]. Within the past few years, preclinical research has suggested a possible neuroprotective benefit from MB administration. MB is believed to promote neuronal cell health by supporting mitochondrial function. Animal studies have yielded promising results in neurocognitive tests[2][3]. Here is what you need to know if you’re interested in using methylene blue.

How does Methylene Blue work?

Mitochondria are organelles within cells that play the key role of energy production. Cellular energy is stored in the form of adenosine triphosphate (ATP), one of the most important molecules in the cell. As the name suggests, ATP contains three linked phosphate groups. Removal of each group releases a large amount of energy, which is expended in supporting cellular function. Subsequent removal of ATP produces ADP (adenosine diphosphate) & AMP (adenosine monophosphate). ATP is produced within mitochondria as a final product of respiration, a series of biochemical reactions that extract energy from glucose. These biochemical reactions require oxygen & electron carriers (e.g. NADH).

Poteet E, Winters A, Yan L, Shufelt K, Green KN, Simpkins JW, et al. Neuroprotective actions of methylene blue & its derivatives. PLoS One. 2012;7(10):e48279-.
Methylene blue acts as an artificial electron carrier, promoting mitochondrial respiration. The net outcome is more energy available as ATP for cellular processes.[4]
Methylene blue supports mitochondrial respiration by functioning as an additional electron carrier[5]. MB receives electrons from NADH through mitochondrial complex I, itself being reduced to leuco-MB (MBH2). Leuco-MB then donates the electrons to cytochrome C, upon which it is recycled back to MB. These reactions serve to create a high proton (H+) concentration in the space between the inner & outer mitochondrial membranes. This leads to the passage of H+ down the concentration gradient, through mitochondrial complex V. In doing so, ADP & a phosphate (Pi) are joined to form ATP. Leuco-MB can also act as a free radical scavenger, neutralising superoxides by accepting electrons & itself becoming oxidized back to MB[6]. In this way, leuco-MB acts to prevent direct oxidative damage caused by free radicals.

Rojas JC, Bruchey AK, Gonzalez-Lima F. Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Prog Neurobiol. 2012 Jan;96(1):32-45.
Methylene blue preferentially accumulates in more active neurones (A), & potentiates mitochondrial & synaptic activity (B). These processes result in increased & improved neurotransmission (C), which is thought to be the mechanism behind the neurocognitive benefits associated with MB.[7]
MB has been observed to preferentially localise in neurones that are more active[3]. Stimulated mitochondria in these neurones modulate genomic expression of proteins that further potentiate mitochondrial respiration via nuclear respiratory transcription factor (NRF-1), resulting in increased expression of cytochrome oxidase (COX), nitric oxide synthase (NOS-1), NMDA receptors, & AMPA receptors. Strengthened synaptic connections as a result of these processes result in improved memory.

The pharmacologic mechanism behind the neuroprotective activity of methylene blue is unique in that it does not involve a receptor-ligand interaction, as do most drugs. In addition, MB also exhibits an atypical dose-response curve– one that has been described as hormetic[8]. Hormesis is a phenomenon where lower doses produce optimum responses while higher doses or exposures may actually produce the opposite effect. Hormesis is an intriguing pattern that may explain the dose-responses associated with exercise & oxidative stress, where the right amount of exercise-induced oxidative stress induces a cascade of favourable physiologic adaptations that can mitigate more severe stressors[9].

Rojas JC, Bruchey AK, Gonzalez-Lima F. Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Prog Neurobiol. 2012 Jan;96(1):32-45.
An example hormetic dose-response curve. Note the inverse response caused with higher doses.[10]
As previously mentioned, metabolism of MB involves reduction to leukomethylene blue (MBH2). MB is primarily eliminated in the urine (75%)[11].

What is it like?

I have tested BlueBrainBoost’s formulation with the following results. I have noticed increased energy and decreased fatigue, with an onset of up to 1 hour and duration of 2-4 hours. The only adverse effects were discolouration of the mouth and urine. I used a dosage of 10 mg (20 drops) in the morning sublingually before brushing my teeth. During this time, I was also taking 30 mg/day coluracetam, 500 mg/day ashwagandha, & 600 mg/day NAC. I suspect that coadministration of CoQ10 and creatine may have a synergistic effect based on the pharmacologic site and mechanism of action.

Is it safe?

methylene blue nootropicMethylene blue is associated with a very favourable safety profile. It is generally well-tolerated at doses lower than 2 mg/kg.[12] The most noticeable side effect of MB is blue discolouration of the oral cavity and blue or blue-green discoloration of the urine. These effects are reversible and not harmful. [13] Staining of the teeth can be removed with repeated tooth-brushing, and discolouration of the urine ceases after the drug is fully removed from the system. Other reported adverse effects include a mild headache and dizziness[14].

MB does exhibit some serotonergic activity. This is due to its inhibition of enzymatic degradation of serotonin by MAO-A. Intravenous doses higher than 5 mg/kg have led to the development of serotonin syndrome. This risk is increased in individuals already taking other serotonergic agents (e.g. tianeptine, St. John’s Wort, common antidepressants, dextromethorphan, tramadol). For these reasons, individuals at risk should avoid coadministration of MB with serotonergic agents by at least 2 weeks (or more depending upon the agent), start at low doses, & increase carefully to an effective dose.

Neurotoxicity has been associated with some preparations of MB as a result of chemical impurities. The presence of heavy metals used in the synthesis of MB can have adverse effects on neurones. Thus, only pharmaceutical grade formulations are recommended for human consumption – not lab grade, & not aquarium grade. These formulations may not meet USP standards and may contain up to 11% contaminants.

How should I take it?

Because MB’s role as a neuroprotective agent in humans is still being studied, there is as yet no recommended dosage. The animal doses used in preclinical trials roughly converts to a human equivalent dose of 0.16–0.64 mg/kg administered sublingually. Sublingual administration may produce higher bioavailability than oral administration, but causes more staining of the mouth. I calculated my dose like so:

  1. 0.16 to 0.64 mg/kg × 54.43 kg = 8.71 mg to 34.84 mg per dose
  2. 10 mg/1 mL = 8.71 mg/x mL → 0.87 mL × 20 gtt/1 mL = 17 gtt to 3.5 mL per dose SL (gtt = drops)

It should be noted that due to the hormetic dose-response curve, the response to MB may decrease with higher doses. MB is typically formulated as a 10 mg/mL solution, where 1 drop = 0.05 mL = 0.5 mg. The bottle should be shaken well before administration.

Summary

Overall, I would recommend methylene blue to individuals looking for an inexpensive extra boost in energy. I have not tested MB long enough to notice changes in cognition or memory, but the pre-clinical studies & pharmacologic literature seem to support this benefit.

  • Methylene blue supports mitochondrial respiration & strengthens synaptic connections, which may lead to decreased fatigue and enhanced cognition & recall. MB exhibits a hormetic dose-response curve.
  • The safety profile has been well-characterised, and MB has generally been shown to be well-tolerated. I believe the most important warnings are those concerning serotonin syndrome and chemical impurities.
  • The best-estimated dosage is only an approximation from animal studies. MB is not yet recommended for human consumption for the purpose of improving cognition and memory.
  • Only pharmaceutical grade formulations of MB should be used.
Methylene Blue
7.5
Focus
8
Mood
7.5
Memory
8
Stimulation
5.5
Relaxation
6.5
Safety
Reviewer 8.3
Summary
Methylene Blue improves mood, memory and energy levels, as well as mitochondrial function (and may also delay aging). I think it is a powerful tool to have in your arsenal, and the BBB solution is cheap and convenient, therefore I highly recommend it to anyone.

References   [ + ]

1. Ginimuge PR, Jyothi SD. Methylene blue: revisited. J Anaesthesiol Clin Pharmacol.
2. Callaway NL, Riha PD, Bruchey AK, Munshi Z, Gonzalez-Lima F. Methylene blue improves brain oxidative metabolism & memory retention in rats. Pharmacol. Biochem. Behav. 2004; 77:175–181.
3, 7. Rojas JC, Bruchey AK, Gonzalez-Lima F. Neurometabolic mechanisms for memory enhancement & neuroprotection of methylene blue. Prog Neurobiol. 2012 Jan;96(1):32-45.
4. Poteet E, Winters A, Yan L, Shufelt K, Green KN, Simpkins JW, et al. Neuroprotective actions of methylene blue & its derivatives. PLoS One. 2012;7(10):e48279-.
5. Gonzalez-Lima F, Barksdale BR, Rojas JC. Mitochondrial respiration as a target for neuroprotection & cognitive enhancement. Biochem Pharmacol. 2014 Apr 15;88(4):584-93.
6. Miclescu A, Basu S, Wiklund L. Methylene blue added to a hypertonic-hyperoncotic solution increases short-term survival in experimental cardiac arrest. Crit. Care Med. 2006; 34:2806–2813.
8. Bruchey AK, Gonzalez-Lima F. Behavioral, physiological, and biochemical hormetic responses to the auto-oxidizable dye methylene blue. Am. J. Pharm. & Toxicol. 2008; 3:72–79.
9. Ji LL, Gomez-Cabrera MC, Vina J. Role of free radicals & antioxidant signaling in skeletal muscle health and pathology. Infect Disord Drug Targets. 2009;9(4):428–444.
10. Rojas JC, Bruchey AK, Gonzalez-Lima F. Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Prog Neurobiol. 2012 Jan;96(1):32-45.
11. Medscape® 5.1.2, (electronic version). Reuters Health Information, New York, New York.
12, 14. Ginimuge PR, Jyothi SD. Methylene blue: revisited. J Anaesthesiol Clin Pharmacol. 2010 Oct;26(4):517-20.
13. Gillett MJ, Burnett JR. Medications and green urine. Intern Med J. 2006 01;36(1):64-6.