FocusNeeds™

In essence, ADD/ADHD is a defect of executive function, much of which resides in the prefrontal cortex (the part of the brain just behind the forehead). ADD/ADHD can be a very serious condition. Many people realize that these conditions often affect the ability to succeed in school, but they are less aware of the many other ways in which these conditions can adversely affect life in many other ways. Decreased attention and increased impulsiveness, both stemming from a difficulty in controlling one’s mind and actions, can lead to many poor decisions. Below are some of the complications demonstrated in research studies as being significant increased in people with ADD/ADHD:

• Increased behavioral risks for poor outcomes:
  • Injuries, traffic accidents, increased health care utilization, obesity, smoking, substance abuse, criminality, unemployment, school dropout, divorce, suicide, unplanned pregnancy, and AIDS risk behaviors.
• Increased mental health risks:
  • Antisocial personality disorder/behaviors, cognitive impairment, autism, schizophrenia, bipolar disorder, major depressive disorder, and tic disorders.

Given the increased risks involved, robust treatment of ADD/ADHD is often advocated and appropriate.

Medical treatments for ADD/ADHD consist of diet and drugs. Multiple dietary nutrients have been shown in studies to be helpful, and since the dosing is generally very high, intervention is generally done by dietary supplementation. Dietary supplementation has the following potential advantages over medications:

• Among the multiple medications often prescribed for ADD/ADHD, many are amphetamines or derivatives thereof. These and most other commonly used drugs for these conditions often have significant side effects. In contrast, dietary supplementation rarely has appreciable side effects.
• The flip side to the many risks of ADD/ADHD are frequent benefits. People with ADD/ADHD are often described as being more creative, interesting, humorous, empathic, spontaneous, courageous, and energetic. These benefits can be lessened or abolished by the medications prescribed. Accordingly, drug therapy often is rejected or reduced in usage by patients. In contrast, dietary supplementation does not appear to reduce these benefits.

In addition, most drugs used commonly to treat ADD/ADHD are stimulants, generally amphetamines or related chemicals that can easily undergo auto-oxidation, forming reactive oxygen species (ROS). Increased ROS is common in mitochondrial dysfunction, and can cause oxidative damage to mitochondria as well as to other cellular components [learn more].

In particular, several reports have demonstrated that methylphenidate has an impact on the generation of oxidative damage. Methylphenidate is a very common drug used for ADD/ADHD, and goes by several different brand names, including Concerta, Daytrana, Metadate, Methylin, Quillivant, and Ritalin [learn more].

Thus, dietary supplementation is often advocated in ADD/ADHD. In mild cases, dietary supplementation may be all that is needed. However, this website should NOT be interpreted to imply that supplementation is a replacement for appropriate medications in all cases. In many cases, supplementation is a good addition to drug therapy. As explained above, ADD/ADHD can be a serious condition, and the appropriate regiment in any given individual may include medication^*.

^*Note that all recommendations on the website are general, and not meant to circumvent or contradict a physician’s advice. It is recommended that ALL treatments be discussed with a physician.

ADD and ADHD are clinical diagnoses that can only be established by an expert following a full evaluation. The official guidelines used by professionals per the guidelines in the American Psychiatric Association's Diagnostic and Statistical Manual, Fifth edition (DSM-5) are abstracted below.

• Inattention: Six or more symptoms of inattention for children up to age 16 years, or five or more for adolescents age 17 years and older and adults; symptoms of inattention have been present for at least 6 months, and they are inappropriate for developmental level:
  • Often fails to give close attention to details or makes careless mistakes in schoolwork, at work, or with other activities.
  • Often has trouble holding attention on tasks or play activities.
  • Often does not seem to listen when spoken to directly.
  • Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g., loses focus, side-tracked).
  • Often has trouble organizing tasks and activities.
  • Often avoids, dislikes, or is reluctant to do tasks that require mental effort over a long period of time (such as schoolwork or homework).
  • Often loses things necessary for tasks and activities (e.g., school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, mobile telephones).
  • Is often easily distracted.
  • Is often forgetful in daily activities.

• Hyperactivity and Impulsivity: Six or more symptoms of hyperactivity-impulsivity for children up to age 16 years, or five or more for adolescents age 17 years and older and adults; symptoms of hyperactivity-impulsivity have been present for at least 6 months to an extent that is disruptive and inappropriate for the person’s developmental level:
  • Often fidgets with or taps hands or feet, or squirms in seat.
  • Often leaves seat in situations when remaining seated is expected.
  • Often runs about or climbs in situations where it is not appropriate (adolescents or adults may be limited to feeling restless).
  • Often unable to play or take part in leisure activities quietly.
  • Is often “on the go” acting as if “driven by a motor”.
  • Often talks excessively.
  • Often blurts out an answer before a question has been completed.
  • Often has trouble waiting their turn.
  • Often interrupts or intrudes on others (e.g., butts into conversations or games).

• In addition, the following conditions must be met:
  • Several inattentive or hyperactive-impulsive symptoms were present before age 12 years.
  • Several symptoms are present in two or more settings, (such as at home, school or work; with friends or relatives; in other activities).
  • There is clear evidence that the symptoms interfere with, or reduce the quality of, social, school, or work functioning.
  • The symptoms are not better explained by another mental disorder (such as a mood disorder, anxiety disorder, dissociative disorder, or a personality disorder). The symptoms do not happen only during the course of schizophrenia or another psychotic disorder.

“ADD” - Predominantly Inattentive Presentation: if enough symptoms of inattention, but not hyperactivity-impulsivity, were present for the past six months.

“ADHD” - Combined Presentation: if enough symptoms of both criteria inattention and hyperactivity-impulsivity were present for the past 6 months.

Link to https://www.psychiatry.org/psychiatrists/practice/dsm

Click on any nutrient to learn more about it.

Component #1: FocusNeeds™-Micronutrition:

Acetyl-L-carnitine/L-carnitine:

Acetyl-L-carnitine was added to FocusNeeds™ because of data in terms of an association between this nutrient and ADHD and good entry into the brain.

• A double-blind, placebo-controlled clinical study on ADHD in fragile X syndrome boys “observed a stronger reduction of hyperactivity and improvement of social behavior” on acetyl-L-carnitine [PMID, 18286595].
• L-carnitine improved total ADHD symptoms measured by the Child Behavior Checklist [PMID 12213433].

Cobalamin (vitamin B12):

Although extensively studied in the related condition of autism, in ADHD the supplementation of cobalamin has not been well studied. Cobalamin was added to FocusNeeds™ because of good data of efficacy in autism, which is a condition highly related to ADD/ADHD.

• Lower vitamin B12 levels were found in several studies in individuals with autism and with ADHD, and a meta-analysis of studies revealed the same (PMID 35034564).

Folate (L-methyltetrahydrofolate, vitamin B9):

Although extensively studied in the related condition of autism, in ADHD the supplementation of folate has not been well studied. Folate was added to FocusNeeds™ because of good data of efficacy in autism, which is a condition highly related to ADD/ADHD.

• SNPs (genetic variants) in the MTHFR are associated with ADHD, especially the A1298C genotype which was associated with a 7.4 fold increased risk, especially of inattentive symptoms, in childhood leukemia survivors [PMID 18154909]. This suggests a possible positive effect of folate in people with ADD/ADHD.

L-theanine:

L-theanine has not been studied in ADD/ADHD yet was added to FocusNeeds™ due to its calming effects without causing sedation. However, L-theanine is sometimes recommended for a variety of conditions including stress/anxiety, insomnia, and ADHD.

• Randomized-controlled trials found L-theanine “may assist in the reduction of stress and anxiety in people exposed to stressful conditions.” [PMID 31758301].
• L-theanine is also often used to improve cognition and focus, an effect of tea drinking that is not solely related to the caffeine content.

Magnesium (magnesium glycinate):

Magnesium was added to FocusNeeds™ because of good data in terms of an association between this nutrient and ADHD.

• In ADHD, a randomized, double blind, placebo-controlled clinical trial in 66 children with ADHD was conducted with a combination of magnesium and vitamin D [PMID 33980185]. On this treatment, significant improvements were noted in emotional problems, conduct problems, peer problems, prosocial score, total difficulties, externalizing score, and internalizing score compared with children on placebo.
• Another randomized, double blind, placebo-controlled clinical trial of children with ADHD supplemented with both magnesium and vitamin D noted “a significant decrease in conduct problems, social problems, and anxiety/shy scores” [PMID 32089804]. Blood levels of both treatments nutrients also improved.
• In another combined treatment, this time with magnesium and vitamin B6, improvement was noted on with in terms of inattention, hyperactivity, and aggressiveness [PMID 16846100]. Low levels of red blood cell magnesium were also noted in the ADHD group, which improved on supplementation.
• In another study [PMID 34474662], children with lower magnesium intake had higher levels of callous-unemotional traits.
• In adults with ADHD, magnesium was shown to have a significant improvement on rating scores [PMID 32162987].
• Finally, in another study [PMID 9368236], magnesium in ADHD was associated with a significant decrease of hyperactivity and an increase in hair magnesium content.

Riboflavin (vitamin B2):

Riboflavin is often used in brain disorders associated with mitochondrial dysfunction, such as autism and migraine. Riboflavin has not been well studied in ADD/ADHD, despite these conditions being well-established to be associated with mitochondrial dysfunction (see the Frequently Asked Questions below). Riboflavin was added to FocusNeeds™ because of the strong association of ADDADHD with abnormal energy metabolism.

• One study noted a lower dietary intake of riboflavin among children with ADHD [PMID 30485932].
• In one study in ADHD adults, lower levels of blood riboflavin were associated with ADHD and the severity of the condition [27990293].

Pyridoxine (vitamin B6, pyridoxyl-5-phosphate, P5P):

Pyridoxyl-5-phosphate was added to FocusNeeds™ because of data in terms of an association between this nutrient and ADHD.

• On combined treatment with vitamin B6 and magnesium, improvement was noted on with in terms of inattention, hyperactivity, and aggressiveness [PMID 16846100].
• In one study in ADHD adults, lower levels of blood B6 were associated with ADHD and the severity of the condition [PMID 27990293].
• Metabolic profiles consistent with B6 deficiency were noted in people with ADHD [PMID 24321736], and per the authors’ retrospective analysis, “multi-year pyridoxine treatment normalizes completely the pattern of ADHD behavior, without causing any serious side effects.”

Vitamin D (vitamin D3, cholecalciferol):

Vitamin D was added to FocusNeeds™ because of good data in terms of an association between this nutrient and ADHD.

• Blood levels of 25-OH-vitamin D are significantly reduced in children with ADHD compared to unaffected children [PMID 24417979, 24610453, 31514566, 33329153, including a meta-analysis (review) of eight other studies 30367389].
• Blood 25-OH-vitamin D is also significantly reduced in the third trimester of pregnancy in children later diagnosed with ADHD [PMID 34534293].
• Reduced vitamin D receptor levels was also reported in ADHD [PMID 29497301].
• In a randomized, double blind, placebo-controlled clinical trial, ADHD symptoms in children improved on vitamin D “with a particular effect on inattention symptoms” [PMID 30456564].
• Another randomized controlled study in children with ADHD was conducted with a combination of vitamin D and magnesium [PMID 33980185]. On this treatment, significant improvements were noted in emotional problems, conduct problems, peer problems, prosocial score, total difficulties, externalizing score, and internalizing score compared with children on placebo.
• Yet another randomized controlled study of children with ADHD supplemented with both vitamin D and magnesium noted “a significant decrease in conduct problems, social problems, and anxiety/shy scores” [PMID 32089804].
• A meta-analysis (review) of four studies using vitamin D as an adjunctive therapy to methylphenidate in ADHD reported that vitamin D supplementation “appeared to reduce ADHD symptoms without serious adverse events, associated with improved vitamin D status” [PMID 31368773]. “(I)mprovement in cognitive function in the conceptual level, inattention, opposition, hyperactivity, and impulsivity domains” was noted with vitamin D in another study on children with ADHD [PMID 29457493].
• ADHD evening symptoms improved with vitamin D supplementation [PMID 27924679].

Zinc (zinc gluconate):

Zinc was added to FocusNeeds™ because of good data in terms of an association between this nutrient and ADHD.

• Low zinc levels were found in the urine and hair of children with ADHD [PMID 35106229].
• A meta-analysis (review) of 21 studies revealed lower blood levels of zinc in ADHD [PMID 34272450].
• In a randomized, double blind, placebo-controlled clinical trial in children with ADHD, impulsivity, hyperactivity, and socialization improved on zinc [PMID 14687872].
• In another controlled trial, zinc was found to be superior to placebo as a supplementary medication to methylphenidate based on the Teacher and Parent ADHD Rating Scale [PMID 15070418].
• In yet another controlled study in ADHD of zinc versus placebo with methylphenidate, improvement on zinc was noted in inattention [PMID 31841818].
• A meta-analysis of six randomized clinical trials in children “showed a significant effect of zinc supplementation on ADHD total scores” and in inattention scores [PMID 34184967].
• Mice fed zinc-deficient diets in early life displayed autism and ADHD-related behaviors such as over-responsivity, hyperactivity, attention deficit, and impairments in vocalization and social behavior, as well as an increased incidence rate of seizures and hypotonia [PMID 24277719].

Component #2: FocusNeeds™-Omega-3:

Omega-3 fatty acids (docosahexaenoic acid, DHA, eicosapentaenoic acid, EPA, with or without phospholipids):

Sources of omega-3 fatty acids (concentrated fish and krill oils) were added to FocusNeeds™ because of good data in terms of an association between these nutrients and ADHD.

• A randomized double-blind, placebo-controlled study revealed improved attention, reduced hyperactive and defiant behaviors, and improvement in cognition and emotion in ADHD children on omega-3 and omega-6 fatty acids [PMID: 11817499].
• Another controlled study reported improved attention and oppositional behaviors in children on predominantly omega-3 fatty acids [PMID: 14669965].
• A third controlled study marked improvement in ADHD symptoms, including improved attention control, and vocabulary performance in children on omega-3 fatty acids as opposed to those receiving placebo [PMID: 17435458].
• Phosphatidylserine (PS)-containing Omega-3 fatty acids were shown to improve ADHD symptoms (impulsivity, inattention), mood and behavioral problems in a controlled study [PMID: 21807480].
• A meta-analysis (an in-depth evaluation comparing multiple studies together) from 2018 [PMID: 28741625] stated “there is evidence that n-3 PUFAs (omega-3) supplementation monotherapy improves clinical symptoms and cognitive performances in children and adolescents with ADHD, and that these youth have a deficiency in n-3 PUFAs levels. Our findings provide further support to the rationale for using n-3 PUFAs as a treatment option for ADHD.”
• An earlier meta-analysis from 2011 [PMID: 21961774] revealed moderate efficacy in comparison to standard drug treatments, yet “given its relatively benign side-effect profile and evidence of modest efficacy, it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacologic interventions or for families who decline other psychopharmacologic options.”
• A review article from 2016 [PMID: 27555775] stated “(i)n conclusion, there is evidence that a ω-3 PUFA (omega-3) treatment has a positive effect on ADHD. It should be added that treatment could be more effective in patients with mild forms of ADHD. Moreover, the dosage of stimulant medication could be reduced when used in combination with ω-3 PUFA supplements.”
• Omega-3 and other natural supplements in ADHD are also summarized in PMID 26966583, 29207548, and recently (2020) 32759851.

Note that not all studies have demonstrated a benefit of the above nutrients, although most did, and some positive studies did not demonstrate improvement in all areas, such as in inattention, impulsivity/hyperactivity, and combined scores.

• Adults and adolescents over 40 kg (> 88 lbs):
  • Two capsules daily of Component #1: FocusNeeds™-Micronutrition,
  • Two soft gel capsules daily of Component #2: FocusNeeds™-Omega-3

Can either be taken at one time or one capsule of each component twice daily.

• Adolescents and children 20-40 kg (44-88 lbs):
  • One capsule daily of Component #1: FocusNeeds™-Micronutrition,
  • One soft gel capsule daily of Component #2: FocusNeeds™-Omega-3
• Children under 20 kg (< 44 lbs):
  • Consult your physician.

We recommend taking this product with meals, at least at first, as gastrointestinal side effects, might occur, including nausea, diarrhea, and/or reflux (GERD).

• 30 days at recommended dosing of two capsules daily of each Component for adults and children over 40 kg (> 88 lbs)
• 60 days at recommended dosing of one capsule daily of each Component for adolescents and children 20-40 kg (44-88 lbs):

Yes, especially in a G (gastrostomy) tube. Absorption in a J (jejunal) tube or GJ-tube may be reduced.

Dr. Boles recommends genetic testing in patients with significant neurodevelopmental disorders, as many times such testing can be helpful in determining the underlying factors leading for disease in that individual, be it mitochondrial dysfunction, neurotransmitter disorders, channelopathy, axonal transport, and/or other mechanisms. Understanding these underlying factors often allows for targeting therapies. Even in patients with known diagnosis, genetic testing can often identify factors leading to disease that suggest specific therapies. For more information, see this link.

The mitochondria are the powerhouse of the cell. Mitochondrial dysfunction indicates that energy metabolism is adversely affected. ADD/ADHD is closely related to autism, which is a neurodevelopmental disorder for which there is much scientific evidence of an association with mitochondrial dysfunction. Many other brain disorders are also known to be associated with mitochondrial dysfunction, including migraine, epilepsy, bipolar, depression, and schizophrenia.

Thus, it is not surprising that ADD/ADHD is also associated with mitochondrial dysfunction. Below is a partial list of the scientific studies supporting this association.

References:

• Lopresti A.L. Oxidative and Nitrosative Stress in ADHD: Possible Causes and the Potential of Antioxidant-Targeted Therapies. ADHD Atten. Deficit Hyperact. Disord. 2015;7:237–247. doi: 10.1007/s12402-015-0170-5 [PMID: 25894292].
• Joseph N., Zhang-James Y., Perl A., Faraone S.V. Oxidative Stress and ADHD: A Meta-Analysis. J. Atten. Disord. 2015;19:915–924. doi: 10.1177/1087054713510354 [PMID: 24232168].
• Nasim, S.; Naeini, A.A.; Najafi, M.; Ghazvini, M.; Hassanzadeh, A. Relationship between Antioxidant Status and Attention Deficit Hyperactivity Disorder among Children. Int. J. Prev. Med. 2019, 10, 41 [PMID: 31057726].
• Bulut, M.; Selek, S.; Gergerlioglu, H.S.; Savas, H.A.; Yilmaz, H.R.; Yuce, M.; Ekici, G. Malondialdehyde Levels in Adult Attention-Deficit Hyperactivity Disorder. J. Psychiatry Neurosci. 2007, 32, 435–438 [PMID: 18043768].
• Bulut, M.; Selek, S.; Bez, Y.; Kaya, M.C.; Günes, M.; Karababa, F.; Çelik, H.; Savas, H.A. Lipid Peroxidation Markers in Adult Attention Deficit Hyperactivity Disorder: New Findings for Oxidative Stress. Psychiatry Res. Neuroimaging 2013, 209, 638–642 [PMID: 23680468].
• Ceylan, M.; Sener, S.; Bayraktar, A.C.; Kavutcu, M. Oxidative Imbalance in Child and Adolescent Patients with Attention-Deficit/Hyperactivity Disorder. Prog. Neuro-Psychopharmacol. Boil. Psychiatry 2010, 34, 1491–1494 [PMID: 20732373].
• Verlaet, A.A.J.; Breynaert, A.; Ceulemans, B.; De Bruyne, T.; Fransen, E.; Pieters, L.; Savelkoul, H.F.J.; Hermans, N. Oxidative Stress and Immune Aberrancies in Attention-Deficit/Hyperactivity Disorder (ADHD): A Case-Control Comparison. Eur. Child Adolesc. Psychiatry 2019, 28, 719–729 [PMID: 30350094].
• Dvoráková, M.; Sivonová, M.; Trebatická, J.; Škodáček, I.; Waczulikova, I.; Muchová, J.; Duračková, Z. The Effect of Polyphenolic Extract from Pine Bark, Pycnogenol® on the Level of Glutathione in Children Suffering from Attention Deficit Hyperactivity Disorder (ADHD). Redox Rep. 2006, 11, 163–172 [PMID: 16984739].
• Leffa, D.T.; Bellaver, B.; De Oliveira, C.; De Macedo, I.C.; De Freitas, J.S.; Grevet, E.H.; Caumo, W.; Rohde, L.A.; Quincozes-Santos, A.; Torres, I.L.S. Increased Oxidative Parameters and Decreased Cytokine Levels in an Animal Model of Attention-Deficit/Hyperactivity Disorder. Neurochem. Res. 2017, 42, 3084–3092 [PMID: 28664398].
• Sezen, H.; Kandemir, H.; Savik, E.; Kandemir, S.B.; Kilicaslan, F.; Bilinc, H.; Aksoy, N. Increased Oxidative Stress in Children with Attention Deficit Hyperactivity Disorder. Redox Rep. 2016, 21, 248–253 [PMID: 26886057].
• Avcil, S.; Uysal, P.; Yenisey, Ç.; Abas, B.I. Elevated Melatonin Levels in Children with Attention Deficit Hyperactivity Disorder: Relationship to Oxidative and Nitrosative Stress. J. Atten. Disord. 2019, 1087054719829816 [PMID: 30819002].
• Selek, S.; Savas, H.A.; Gergerlioglu, H.S.; Bulut, M.; Yilmaz, H.R.; Yılmaz, H.R. Oxidative Imbalance in Adult Attention deficit/hyperactivity disorder. Boil. Psychol. 2008, 79, 256–259 [PMID: 18644422].
• Ceylan, M.F.; Sener, S.; Bayraktar, A.C.; Kavutcu, M. Changes in Oxidative Stress and Cellular Immunity Serum Markers in Attention-Deficit/Hyperactivity Disorder. Psychiatry Clin. Neurosci. 2012, 66, 220–226 [PMID: 22443244].

Most drugs used commonly to treat ADD/ADHD are stimulants, generally amphetamines or related chemicals. These drugs increase catecholamine neurotransmitters levels, including dopamine and norepinephrine. However, these neurotransmitters can easily undergo auto-oxidation, forming reactive oxygen species (ROS). Increased ROS is common in mitochondrial dysfunction, and can cause oxidative damage to the mitochondria and other cellular components.

In particular, several reports have demonstrated that methylphenidate has an impact on the generation of oxidative damage. Methylphenidate is a very common drug used for ADD/ADHD, and goes by several different brand names, including Concerta, Daytrana, Metadate, Methylin, Quillivant, and Ritalin.

References:

• Alvarez-Arellano, L.; et al. Antioxidants 2020, 9, 176; doi:10.3390/antiox9020176 – Review [PMID: 32098021].
• Goldstein, D.S.; et al. Pharmacol. Ther. 2014, 144, 268–282 [PMID: 24945828].
• Napolitano, A.; et al. Curr. Med. Chem. 2011, 18, 1832–1845 [PMID: 21466469].
• Neri, M.; et al. J. Cell. Mol. Med. 2007, 11, 156–170 [PMID: 17367510].
• Spencer, W.A.; et al. Free Radic. Biol. Med. 2011, 50, 139–147 [PMID: 21075203].
• Swanson, C.J.; et al. Neuropharmacology. 2006, 50, 755–760 [PMID: 16427661].
• Bymaster, F.; et al. Neuropsychopharmacology 2002, 27, 699–711 [PMID: 12431845].
• Alvarez-Arellano, L.; et al. Antioxidants (Basel). 2020 Feb; 9(2): 176. [PMID: 32098021].
• Andreazza, A.C.; et al. Prog. Neuro-Psychopharmacol. Boil. Psychiatry 2007, 31, 1282–1288 [PMID: 17614179].
• Martins, M.R.; et al. Brain Res. 2006, 1078, 189–197 [PMID: 16494852].
• Gomes, K.M.; et al. Neurochem Res. 2008, 33, 1024–1027 [PMID: 18049893].
• Comim, C.M.; et al. Acta Neuropsychiatr. 2014, 26, 96–103 [PMID: 24855887].
• Motaghinejad, M. et al. J. Neural Transm. 2017, 124, 121–131 [PMID: 27682635].

• Mitochondrial dysfunction is very common in people with neurodevelopmental disorders, including ADD/ADHD. In addition, many of the common medications used to treat this condition, including stimulants, can cause acquired mitochondrial dysfunction. Since all cells need energy to perform almost all functions, mitochondrial dysfunction can present in many different ways. However, nerve cells are electrical and have high energy demands. Thus, mitochondrial dysfunction generally, but not always, presents as neurological disease, including brain disorders.

  How do you know if you or your child has mitochondrial dysfunction? While there is no simple answer to this, there are some conditions which are commonly seen. Suspect mitochondrial dysfunction if there are two or more of the following:

  • ADD/ADHD
  • Autistic spectrum disorder/pervasive developmental disorder
  • Loss of milestones/regression
  • Movement disorder (including ataxia, dystonia, chorea, tics)
  • Stroke or stroke-like episodes
  • Myopathy (muscle disease), especially ocular (eye) or cardiac (heart)
  • Chronic bowel dysmotility (especially if severe or at more than one level)
  • Cyclic vomiting
  • Dysautonomia (including POTS, frequent tachycardia, unexplained fevers)
  • Chronic pain condition (including migraine, muscle pain)
  • Chronic fatigue or exercise intolerance
  • Mood disorders (depression, anxiety, etc.)
  • Waxing and waning clinical course (including altered mental status or psychosis)
  • Hypoglycemia
  • Metabolic acidosis (either renal tubular loss and/or anion gap)
  • Elevated liver transaminases (including only trace elevated, if frequent)

   

  There is no single excellent laboratory testing to document or rule out mitochondrial dysfunction in most cases. Biochemical, enzymatic, imaging, and/or genetic testing are sometimes used following consultation with an expert.

  The treatment of mitochondrial dysfunction predominantly includes dietary supplementation with various natural vitamins, minerals, cofactors, antioxidants, and other nutrients to both support mitochondrial function and to remove excessive products of abnormal oxidative metabolism (e.g., ROS). These nutrients are often referred to colloquially as the “mitochondrial cocktail”.

  Mitochondrial dysfunction is common in ADD/ADHD and is treatable. Thus, FocusNeeds™ contains some of the most commonly recommended and important components of the mitochondrial cocktail, including acetyl-L-carnitine, riboflavin (vitamin B2), cobalamin (vitamin B12), vitamin D, magnesium, and zinc. In many people with ADD/ADHD, the mitochondrial cocktail in FocusNeeds™ is sufficient, particularly in mild cases and in cases that respond well to treatment. However, in more severe cases and in those not responding adequately to treatment, a more robust mitochondrial cocktail with additional ingredients should be considered.

  EnergyNeeds®, SpectrumNeeds®, and QNeeds® are NeuroNeeds® products that provide a powerful mitochondrial cocktail. See the next FAQ to learn more about them.

   

  
  

   

• Other Frequently Asked Questions just above in the list discuss that:

  • Mitochondrial dysfunction is common in ADD/ADHD.
  • Stimulant medications commonly used to treat ADD/ADHD often themselves can cause mitochondrial dysfunction.
  • Mitochondrial dysfunction can present in many ways.
  • Mitochondrial dysfunction is treatable by various all-natural vitamins, minerals, cofactors, antioxidants, and other nutrients (“mitochondrial cocktail”).

  In Dr. Boles’ experience, treatment of ADD/ADHD with mitochondrial cocktail can often result in substantial improvement, including in his own son. Because of excellent response and mild to no side effects, Dr. Boles strongly recommends mitochondrial cocktail in his patients with ADD/ADHD.

  NeuroNeeds® produces products that provide a powerful mitochondrial cocktail:

  • EnergyNeeds®: 40 active ingredients, most of which are components of the mitochondrial cocktail, the others are predominantly nutrients such that EnergyNeeds® can substitute for a comprehensive multivitamin and mineral supplement. This product is in a capsule form.
  • SpectrumNeeds®: Very similar to EnergyNeeds®, but 33 active ingredients in a powder form. SpectrumNeeds® comes in two flavors, Lemon and Berry.
  • QNeeds®: Contains ubiquinol, the highly bioavailable (chemically reduced) coenzyme Q10 (coQ10), in limonene oil. CoQ10 is a strong antioxidant that has shown benefit in a study in autism (PMID: 24707344) and thus also may help in ADD/ADHD. Dr. Boles strongly recommends coQ10 in his patients with neurodevelopmental disorders, including ADD/ADHD.

  People vary in terms of the severity of inattention, the presence and type of other health issues, personal finances, and willingness to take multiple different products each day. Thus, NeuroNeeds® has created two different paths to better focus:

  Silver Path = FocusNeeds™:

  • Only one inexpensive product to buy.
  • Good for people with less-severe variations of ADD/ADHD.
  • Great for people without a diagnosis or any illness that would like to improve their focus in work, school, or life.
  • Contains several components of the mitochondrial cocktail for moderate mitochondrial support.
  • Can be subsidized if needed with ubiquinol/CoQ10 (e.g., QNeeds®) and/or extra magnesium (about 250-500 mg per day).

  Gold Path = EnergyNeeds® + OmegaNeeds® + QNeeds®:

  • Three products:
    • EnergyNeeds® covers the active ingredients in Component #1: FocusNeeds™-Micronutrition, plus multiple additional components in order to constitute a high-powered, broad-spectrum mitochondrial cocktail, plus a robust multivitamin and mineral supplement.
    • OmegaNeeds® contains fish and krill oils; identical to Component #2: FocusNeeds™-Omega-3.
    • QNeeds® consists of ubiquinol (highly bioavailable coenzyme Q10, a strong antioxidant) in limonene oil.
  • Higher costs, although can be purchased as a cost-saving bundle.
  • Good for people with more-severe variations of ADD/ADHD, those with other neurodevelopmental disorders (e.g., autism), and those with other conditions whereas mitochondrial dysfunction is common (e.g., depression, significant anxiety, chronic fatigue, chronic pain).
  • Contains over 20 components of the mitochondrial cocktail for excellent mitochondrial support.
  • Can be subsidized if needed, including with extra magnesium (about 250-500 mg per day).

   

   

   

   

• Anyone interested in good brain health. The omega-3 fatty acids present in FocusNeeds™ have been shown in studies to be helpful in people with multiple disorders of the brain, including ADD/ADHD, autism, migraine, depression, anxiety, chronic pain, and dementia.
• Anyone interested in good heart health. The omega-3 fatty acids present in FocusNeeds™ have been shown in studies to be helpful in people with multiple disorders of the heart and blood vessels, including reduction of blood pressure, improved lipid (cholesterol, triglyceride) levels, weight control, and protection against cardiovascular disease (e.g., heart attack).
• Anyone interested in good general health. The omega-3 fatty acids present in FocusNeeds™ have been shown in studies to be helpful with inflammation, autoimmune disease, diabetes/blood sugar, macular degeneration (age-related blindness), and in many other conditions, see list below.

Selected studies and reviews demonstrating relationships between omega-3 fatty acids in various conditions (Library of Congress PMID listings shown):

• ADHD 11817499, 14669965, 17435458, 21807480, 21961774, 26966583, 27555775 28741625, 29207548, 32759851
• Anxiety 21784145, 30646157, 34959972
• Autism 11487301, 16920077, 18072818, 22370992, 24839884, 28218722, 29490101, 30744880, 32759851
• Autoimmune disease 12480795, 15290734 (lupus), 15723739 (RA), 26362904 (MS)
• Cardiovascular disease/blood lipids 11997274, 18774613, 19487105, 22113870, 22180524, 22317966, 25458786
• Depression/bipolar 12888186, 15907142 (multiple psychiatric disorders), 17685742, 18247193, 21721919, 22910528, 24757497, 26188642
• Dementia 19262590, 19523795, 25592004, 28466678
• Diabetes (especially autoimmune-related) 14668274, 25329601, 30684965
• Inflammation 12480795, 20727522, 21784145, 24505395
• Macular degeneration 24557349, 34749130, 34829613
• Metabolic syndrome 19593941, 20727522, 23456976
• Pain 7588501, 8623866, 24049587, 28495596
• Skin disorders 20620762, 21760742, 34681353
• Sleep disorders 21897776, 24605819, 24812543

The above list constituents only a small number of the vast number of studies that have been published on omega-3 fatty acids in health. Not all studies have shown a benefit. Nutrients are used frequently by others in the treatment of a variety of conditions, and inclusion herein does NOT reflect a recommendation or endorsement for treatment of that condition, but simply demonstrates that at least one medical/scientific paper found potential benefit. Please consult your physician and/or seek additional sources as appropriate.

While there are several omega-3 fatty acids, DHA and EPA are particularly important, and receive by far the most attention, in terms of supplementation in health and disease. These fatty acids are critical for membrane fluidity and other properties.

Docosahexaenoic acid (DHA; 22:6n3) is the most abundant polyunsaturated (two or more double bonds) fatty acid in the brain. Most of brain DHA is esterified (a type of chemical bond) to phospholipids located in membranes, predominately as phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE). DHA is located throughout the brain, with relatively higher concentrations in gray matter and especially at synapses. DHA has many beneficial effects on health, and is essential for brain development, learning, and vision. DHA levels in the brain rapidly increase around the time of birth and in the first two years thereafter.

DHA is involved in numerous processes in the brain, including the maintenance of membrane fluidity, neuronal survival, synaptic neurotransmission, and neuroinflammation. Thus, it is not surprising that disturbances in brain DHA metabolism have been implicated in multiple neurological disorders, including those considered to be neurodegenerative and psychiatric. Among these disorders are autism, ADHD, bipolar disorder, depression, epilepsy, Alzheimer, Parkinson disease, and cerebral ischemia (from stroke, heart attack, drowning, etc.). A potential role of DHA in the prevention of these and other neurological disorders has been advocated. In rats with cerebral ischemia, DHA improves neurological functions and decreases the degree of brain damage visible by microscopy [PMID: 19542051].

Eicosapentaenoic acid (EPA; 20:5n3) is present in brain only at very low levels. However, EPA is converted into DHA in the brain. EPA is becoming increasingly recognized as important for brain in health and disease. The use of EPA has less studied the DHA in various neurological conditions. “Although DHA appears more effective for neuroinflammatory conditions, EPA is more beneficial for depression” [PMID: 30530735]. Most studies have used the two together, and they naturally occur together in products derived from both fish and krill oil.

In humans and other vertebrates, most fatty acids are part of triglycerides, often referred to simply as “fat”. A triglyceride consists of three fatty acids, which can be of the same or different types, bound to glycerol (a 3-carbon alcohol). Phospholipid are another type of fat in which one of the end carbons of glycerol is bound to a compounded phosphate and the other two carbons are bound to fatty acids. Usually, the phosphate is compounded with choline, serine, inositol, or ethanolamine, and these fats are referred to as phosphatidylcholine (often abbreviated as PC), phosphatidylserine (PS), phosphatidylinositol (PI), or phosphatidylethanolamine (PE), respectively. The two fatty acids can be the same of different types and can be omega-3 fatty acids. Phospholipids are critical in many processes, including in mitochondrial energy metabolism, and in many aspects of health, especially in the brain and heart.

Alpha-linolenic acid (ALA, C18:3n3) is an important omega-3, essential fatty acid. Humans can convert ALA to EPA. Humans can then convert EPA to DHA. However, brain has very limited capacity to synthesize DHA and ≤ 0.2% of the ALA entering the brain is converted to DHA. Almost all DHA and EPA in the brain is imported from the blood. While human liver has the ability to convert ALA to EPA to DHA, a major limitation is that all these omega-3s are essential. We cannot make ALA (except from other omega-3s such as EPA), and ALA is one of the main essential fatty acids that we obtain from plants. Humans can interconvert ALA, EPA, and DHA, but cannot put the double bond into the omega-3 position. These fatty acids must come from the diet. For people whose diet is low in fruits, vegetables, and seafoods, all these omega-3 fatty acids can be deficient. Thus, while we can interconvert these fatty acids, the omega-3s in general must come from the diet.

The main sources for EPA and DHA are from algae, either directly or indirectly. Western diets usually are low on algae. Since algae is the main base of the oceanic food chain, seafood is high in omega-3 fatty acids from algae. Cold-water oceanic animals are particularly rich in omega-3 fatty acids, which become increasingly concentrated in organisms the further they are up the food chain. Some fish can also source omega-3s from their own gut flora. Thus, the main dietary source of omega-3s in most Western populations is from seafood.

Thus, a diet rich in seafood is an excellent source of omega-3s. However, seafood can be contaminated by mercury and other heavy metals, in which concentrations also accumulate up the food chain. Additionally, seafood is expensive, not available everywhere, and not preferred by many people. Also, there are issues regarding the sustainability of massive fishing on natural marine populations. For these reasons, seafood-derived oils, either from small oily fishes (mackerel, anchovies, herring, sardine) or crustaceans (krill), is preferred. Good sources are high in omega-3 fatty acids, very low in mercury and other heavy metals, and sustainably fished. OmegaNeeds® is one such source.

Phospholipids are particularly abundant in krill, in which most of the EPA and DHA are complexed as part of phospholipids.

There are two major mechanisms in which most omega-3 fatty acids enter brain. This has been studied more extensively for DHA.

1. Passive diffusion across the cell membrane
2. MFSD2A-mediated transport

Cell membranes are composed mostly of lipids, for which fatty acids are a major component. DHA from the blood can directly enter the outside side of a cell membrane, “flip” over to the inner side of the membrane, then disassociate from the membrane to enter the cell. This transport by “passive diffusion” occurs from areas of high concentration to areas of low concentration. By passive diffusion, the tissue concentration in brain, heart, or other organs cannot exceed that of the blood by this mechanism. Thus, to increase tissue concentrations beyond usual levels, very high blood levels are needed. This is exactly the mechanism by which many of the premium, high-potency omega-3 fatty acid products on the market work. These products contain very high amounts of omega-3 fatty acids in order to substantially raise the concentration in the blood, and thus to raise the concentration in the tissues.

However, most of the DHA in the brain enters by way of the MFSD2A system [PMID: 24828044]. MFSD2A is expressed exclusively on the endothelium of the blood-brain barrier, whereas it is found at high concentration. The blood-brain barrier consists of the cells lining the blood vessels within the brain, which fit tightly together limiting transport into brain in order to protect this vital organ. Mice lacking MFSD2A have markedly reduced levels of DHA in brain and loss of neurons (nerve cells) in important brain areas such as the hippocampus and cerebellum. These mice have cognitive deficits (mental retardation), severe anxiety, and small heads. Humans born with genetic mutations in MFSD2A have cognitive deficits, small heads, spasticity, seizures, and early death [PMID: 26005865, PMID: 26005868]. Brain imaging usually shows abnormalities related to a loss of neurons, and cellular studies showed much reduced DHA transport rates [PMID: 26005868]. Additionally, mice with genetic mutations that remove MFSD2A function have 50% lower brain DHA levels when compared to littermates without the mutation, attributed to significantly reduced brain DHA uptake [PMID: 24828044].

Studies demonstrate that over 80% of DHA in the body is esterified (a form of chemical bond) in phospholipids [PMID: 24036166]. MFSD2A transports DHA into brain only if esterified in phospholipid, in particular phosphatidylcholine (PC), but also phosphatidylserine (PS) and phosphatidylethanolamine. However, MFSD2A transports very little DHA into brain if esterified in triglycerides or unesterified (by itself, free fatty acids) [PMID: 24828044]. Omega-3 fatty acids, including DHA, are naturally esterified with PC in products derived from krill. Thus, krill-based products have a substantial advantage in terms of promoting brain uptake of DHA. On the other hand, brain DHA uptake is more difficult when present in triglycerides, as is the case with products derived from fish. Blood DHA levels must be highly elevated in order to facilitate brain uptake from passive diffusion

EPA esterified in PC (PC-EPA) was shown to increase brain EPA levels over 100-fold, while free EPA had little effect. “Furthermore, LPC-EPA, but not free EPA, increased brain DHA 2-fold” [PMID: 30530735]. Krill oil, and FocusNeeds™, contain high amounts of PC-EPA.

Supplementation with the omega-3 fatty acids DHA and/or EPA has shown modest success in controlling symptoms related to ADHD. While not all studies have demonstrated a benefit, most did, including the randomized, placebo-controlled trials summarized here:

• Improved attention, reduced hyperactive and defiant behaviors, and improvement in cognition and emotion in ADHD children on DHA 480 mg/day, EPA 186 mg/day, and additional nutrients (gamma-linolenic acid 96 mg, vitamin E 60 IU, cis-linoleic acid 864 mg, arachidonic acid 42 mg, and thyme oil 8 mg) [PMID: 11817499].
• Improved attention and oppositional behaviors in children on DHA 480 mg, EPA 80 mg, arachidonic acid 40 mg, gamma-linolenic acid 96 mg, and vitamin E 24 mg [PMID: 14669965].
• Marked improvement in ADHD symptoms, including improved attention control, and vocabulary performance in children supplemented for 15 weeks with EPA as opposed to those receiving placebo [PMID: 17435458].
• Improvement of ADHD symptoms (impulsivity, inattention), mood and behavioral problems on phosphatidylserine (PS) containing 120 mg total EPA and DHA [PMID: 21807480].

Additional references discussing omega-3 therapy in ADHD:

• A meta-analysis (an in-depth evaluation comparing multiple studies together) from 2018 [PMID: 28741625] stated “there is evidence that n-3 PUFAs (omega-3) supplementation monotherapy improves clinical symptoms and cognitive performances in children and adolescents with ADHD, and that these youth have a deficiency in n-3 PUFAs levels. Our findings provide further support to the rationale for using n-3 PUFAs as a treatment option for ADHD.”
• An earlier meta-analysis from 2011 [PMID: 21961774] revealed moderate efficacy in comparison to standard drug treatments, yet “given its relatively benign side-effect profile and evidence of modest efficacy, it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacologic interventions or for families who decline other psychopharmacologic options.”
• A review article from 2016 [PMID: 27555775] stated “(i)n conclusion, there is evidence that a ω-3 PUFA (omega-3) treatment has a positive effect on ADHD. It should be added that treatment could be more effective in patients with mild forms of ADHD. Moreover, the dosage of stimulant medication could be reduced when used in combination with ω-3 PUFA supplements.”
• Omega-3 and other natural supplements in ADHD are also summarized in PMID 26966583, 29207548, and recently (2020) 32759851.

Medications are often effective and appropriate in the treatment of behavioral over-activity, and in particular in ADHD can sometimes help get a failing student back on track again. NeuroNeeds® does not advocate nutrition over medication in all or most cases. However, appropriate nutritional therapies can often be an effective complementary approach along with appropriate medical therapies. OmegaNeeds® can be an important part of nutritional therapy in people with ADHD. Also, consider adding mitochondrial support in the form of SpectrumNeeds® (capsules, 40 active ingredients) or EnergyNeeds® (powder, 2 flavors, 33 active ingredients), in addition to QNeeds® (gel capsules, highly bioavailable ubiquinol form of coenzyme Q10). In Dr. Boles’ experience, nutritional therapies can sometimes reduce the amount of dosage of medication needed, and occasionally eliminate the needs for medications altogether. In addition, medications are not appropriate in all affected individuals.

The U.S. Environmental Protection Agency (EPA) states that 0.1 mcg of mercury per kg of body weight per day is the maximum safe dose. This is 7 mcg (micrograms) for a 70 kg (155 lb) man. The oils used in FocusNeeds™ are very low in mercury, which is certified by testing to be below 0.1 mg/kg of oil. The recommended adult daily amount of FocusNeeds™ contains 2.0 grams of seafood oils, which contains less than 2 mcg of mercury. In comparison, for canned tuna (about 0.13 ppm (parts per million) of mercury), the same 2 mcg of mercury is found in about 16 grams of fish, or about 3 teaspoons. Swordfish has 1.0 ppm of mercury, such that 2 mcg corresponds to 2 grams of fish, less than half a teaspoon!

Arsenic, cadmium, and lead levels are also very low (maximum 0.1 mg/kg of oil). Microbial counts are low to absent, including yeast, mold, coliforms, salmonella, and Staph aureus.