Scientific Evidence on FocusNeeds® Ingredients

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.