Part IV - Alternative Treatments and ADHD - Sweeteners

Sweeteners

     Another topic of investigation within the ADHD world, has been the connection between sugar and behavior. Some parents and researchers have claimed that sugar is one of the key factors in the onset, severity and continuation of symptoms with children diagnosed with ADHD. However, yet again, a glimpse of the evidence is important before assuming this claim as true. A 1994 double-blind controlled trial of 48 children was conducted to investigate the role of sugar in behaviorally and cognitively challenged children (per parent report).^M Twenty-five of the children were considered the control group, with no reported sensitivities to sugar and 23 of the children were classified as having sugar sensitivities.^M All of the children underwent three consecutive three-week trials of differing sweetener combinations, the first consisting of sucrose only with no artificial sweeteners, the second consisting of low sucrose levels and mostly aspartame sweeteners, and the third consisting of saccharin (placebo).^M The researchers controlled for variables such as preservatives, artificial dyes, and additives which are oftentimes blamed for additional behavioral and cognitive complications.^M Outcomes of the study showed no difference among groups.^M In addition to the fact that no effect was observed, the researchers further stated that even when intake of the listed sweeteners exceeded normal dietary levels, the effect remained unsubstantial.^M Similarly, in a randomized, double-blind, placebo-controlled crossover study, researchers examined the effects of heightened doses of aspartame on the behavior and cognition of children labeled with the ADD diagnosis.^N Children were given aspartame or placebo for alternate 2-week periods to determine effect.^N Outcomes of this study showed no clinically significant differences between the placebo and aspartame administrations in regard to symptoms, behavior or cognition.^N Though not as reliable as controlled research studies, anecdotal evidence has suggested that there is a relationship between sugar intake and hyperactive behaviors.^O A 1994 research study looking at the connection between sugar intake and hyperactive behavior in children showed that sweeteners do not affect behavior.^O This particular study examined the differences between diets high in sucrose, aspartame, and saccharin and found that even when doses exceeded normal intake levels, no differences were observed in hyperactivity.^O Similarly, a 1991 study looked at the difference between a sugar-sweetened diet compared to a saccharin/aspartame-sweetened diet (placebo).^P Subjects in the study group were 17 children diagnosed with ADHD and were compared to the control group of 9 children without the ADHD diagnosis.^P Results showed no difference in levels of aggression between the study and control groups.^P Despite this finding, children with the ADHD diagnosis did show increased inattention following sugar ingestion when compared to the control group.^P However, the researchers stated in conclusion, “This result is of questionable clinical significance inasmuch as aggressive behavior was unchanged. The finding may be due to the combination of the sugar challenge with a high-carbohydrate breakfast. These findings should be replicated and any possible clinical significance should be documented before any dietary recommendations can be made.”^P Again, though the elimination of sugar may have a positive effect on some ADHD-diagnosed children, the apparent evidence is not overwhelming.

References

M. Wolraich ML, Lindgren SD, Stumbo PJ, et al. Effects of diets high in sucrose or aspartame on the behavior and cognitive performance of children. The New England Journal of Medicine. 1994; 330: 301-306. 

N. Shaywitz BA, Sullivan CM, Anderson GM, et al. Aspartame, behavior, and cognitive function in children with attention deficit disorder. Pediatrics. 1994; 93:70-75.

O. Kanarek RB. Does sucrose or aspartame cause hyperactivity in children? Nutrition Reviews. 1994; 52: 173-175.

P. Wender EH, Solanto MV. Effects of sugar on aggressive and inattentive behavior in children with attention deficit disorder with hyperactivity and normal children. Pediatrics. 1991; 88: 960-966.

Part III - Alternative Treatments and ADHD - Multivitamins

Multivitamins

     Though it has been suggested that vitamin and nutrient deficiencies can lead to significant cognitive impairment and declined performance on intelligence tests, the assumption that such supplementation may subsequently aid children diagnosed with ADHD has not been proven with extensive and convincing research data.^H Adequate research studies with large sample sizes, sufficient trial times and randomized controls appears lacking in the investigation of the role of multivitamins in relation to ADHD.  Some studies have shown preliminary evidence of benefit for adults taking multivitamin supplements to treat ADHD symptoms, yet caution to accept efficacy is warranted due limitations such as small sample size and short-term trials.^I  During an 8-week trial, 14 adults diagnosed with ADHD were observed while taking a 36-ingredient micronutrient formula.^J Though results showed improvement of symptoms, the effects are questionable at best due to the small sample size, short trial length and method of evaluation (self, clinician and observer reports).^J In addition, researchers admitted that due to the limitations of this study design, the outcome  “does not in itself prove efficacy”.^J Research studies involving children have been performed with some level of similarity, yet also with notable limitations. A fully blinded, randomized, placebo-controlled trial looked at 93 children with the ADHD diagnosis and tested the efficacy of multivitamin supplementation on symptoms.^K Results indicated that subjects receiving vitamin and mineral supplementation improved in overall function, including reduced impairment and improved attention but did not show reduced levels of hyperactive and impulsive symptoms when compared with the control group.^K The researchers subsequently commented that, “Although direct benefit for core ADHD symptoms was modest, with mixed findings across raters, the low rate of adverse effects and the benefits reported across multiple areas of functioning indicate micronutrients may be a favourable option for some children, particularly those with both ADHD and emotional dysregulation.”^K Therefore, though these findings point to potential benefit, they do not provide overwhelming evidence for efficacy at this time. In addition, though some benefit was found, it was mild and did not address all levels of the symptom profile, namely the hyperactive and impulsive actions that frequently are the most challenging to deal with in such cases. Some research studies have performed trials with ADHD-diagnosed children to determine if deficiencies in vitamin and hormone levels exist. By investigating deficiencies, such studies have attempted to suggest the importance of supplementation in these populations. In a 2014 study of 77 kids, researchers looked at levels of ferratin, vitamin D, vitamin B12, adrenal and gonadal steroid levels, celiac antibodies, and thyroid hormones and antibodies.^L Subjects were divided into three groups: children with the ADHD diagnosis, children with the Asperger’s diagnosis, and children with no diagnosis (control group).^L Deficiencies were found in both diagnosed categories when compared with the control group, thus leading the researchers to conclude that vitamin D and B12 supplements would benefit these populations.^L Despite the observed levels of deficiency, however, this study did not investigate the outcome of ADHD-diagnosed children taking these vitamins, thus bringing into question the validity of the claim of likely efficacy.

References

H. Benton D. Symposium on nutrition and cognitive efficiency. Proceedings of the Nutrition Society. 1992; 51: 295-302.

I. Rucklidge JJ, Framptom CM, Gorman B, Boggis A. Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial. The British Journal of Psychiatry. 2014; 204: 306-315.

J. Rucklidge JJ, Taylor M, Whitehead K. Effect of micronutrients on behavior and mood in adults with ADHD: evidence from an 8-week open label trial with natural extension. Journal of Attention Disorders. 2011; 15:79-91.

K. Rucklidge JJ, Eggleston MJ, Johnstone JM, Darling K, Frampton CM. Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial. Journal of Child Psychology and Psychiatry, and Allied Disciplines. Published Online: October 2, 2017 (doi: 10.1111/jcpp.12817).

L. Bala KA, Dogan M, Mutluer T, Aslan O, Dogan SZ. Hormone disorder and vitamin deficiency in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs). Journal of Pediatric Endocrinology and Metabolism. 2016; 29: 1077-1082.

Part II - Alternative Treatments and ADHD - Magnesium

     Magnesium

     Another supplement frequently recommended as an alternative or adjunctive treatment for ADHD is magnesium. An initial look at the research gives reason to believe that magnesium supplementation may offer some treatment benefit. In a 1997 research study on the effectiveness of magnesium supplementation in hyperactive children, 50 subjects ages 7-12 were observed over the course of 6 months.^E At the conclusion of the 6 month trial period, the test group showed increased levels of magnesium as well as decreased incidence of hyperactivity when compared to the control group.^E The small sample size may pose a limitation to the outcome of this study. With similar findings, a longitudinal, observational study was conducted in Germany with 810 children ages 5-12 over the course of 3 months.^F Results showed that when subjects were given Esprico (a food supplement combining omega 3, omega 6, zinc and magnesium), they experienced substantial reductions in ADHD symptoms, emotional and behavioral problems and sleep challenges.^F Once again, significant limitations to this study exist. A drop-out rate of 14% was noted due to absence of positive effect, lack of compliance or adverse reactions.^F Further, 7.3% of the subjects were taking other medications or involved in alternate treatment as well, such as medications for obstructive pulmonary disease, thyroid therapeutics, psycho stimulants, unspecified amphetamines, non-stimulant medication and homeopathic remedies.^F In addition, the study did not provide a control group, posing considerable limitation to the reliability of the research outcomes.^F Perhaps most significant of the limitations of this study is the fact that it was funded by a grant from Engelhard Arneimittel, a German Pharmaceutical company, likely leading to investigator bias. A review of the literature regarding magnesium supplementation in children with the ADHD diagnosis can shed light on the problematic nature of stating that magnesium is an effective treatment for this disorder. Esparham et al. reviewed multiple articles in the efficacy of magnesium supplementation in ADHD-diagnosed children.^G Though a summary of the study outcomes showed benefit with this therapy, a marked number of limitations were present across the studies.^G Systematic review revealed that the majority of the studies had methodological limitations such as lack of double-blind randomized controlled study design and lack of measurement standardization in regard to the levels of magnesium.^G The general outcome of these studies may, at best, offer reason to investigate this treatment modality in future research. 

References

D. Moghaddam MF, Shamekhi M, Rakshani T. Effectiveness of methylphenidate and PUFA for the treatment of patients with ADHD: a double-blinded randomized clinical trial. Electronic Physician. 2017; 9: 4412-4418. Available from: http://www.ephysician.ir. Accessed December 15, 2017.

E. Starobrat-Hermelin B, Kozielec T. The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnesium Research. 1997; 10: 149-156.

F. Huss M, Volp A, Strauss-Grabo M. Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit/hyperactivity problems – an observational cohort study. Lipids in Health and Disease. 2010; 9: 105-117.

G. Esparham A, Evans RG, Wagner LE, Drisko JA. Pediatric integrative medicine approaches to attention deficit hyperactivity disorder (ADHD). Children. 2014; 1: 186-207.

Part 1 - Alternative Treatments and ADHD - Omega 3/Fish Oil

 Omega 3 Fatty Acids and Fish Oil

     Consistent disagreement remains in the discussion regarding the benefit of including Omega 3 fatty acids or fish oil in the diets of those suffering from ADHD, yet the majority of evidence seems to support the conclusion that this supplement is questionable at best.  A 2016 study examined the effects of a marine oil extract on the levels of hyperactivity, inattention, cognition, and mood in children.^A Researchers discovered that the ingestion of such supplementation did not result in the improvement of parental reports in regard to hyperactivity, inattention and impulsivity, though some positive effect was seen in children without the ADHD diagnosis.^A  Additionally, extensive review articles can be found on the subject, comparing numerous studies on this topic.  In a review of 16 randomized controlled trials including 1,514 youth with the ADHD diagnosis, overall conclusions displayed that the use of Omega-3/6 supplementation had promising effects and could be effectively used as adjunctive therapy to the more traditional approaches.^A  However, this review has significant limitations as the authors were funded by Equazen, a company that manufactures Omega-3/6 supplements, thus likely bringing significant bias into the findings.^B Another review considered multiple studies investigating the benefits of Omega-3 supplementation in children labeled with the ADHD diagnosis and found multiple discrepancies among those examined.^C Lack of placebo groups, small sample sizes, and minimal trial length contributed to the inconsistencies of the studies and subsequent lack of reliability.^C  In a study investigating the effectiveness of Omega 3 supplementation used in conjunction with methylphenidate (a drug commonly prescribed for ADHD), researchers concluded that the Omega 3 addition provided subjects with significantly better outcomes when compared with controls.^D Though this double-blinded randomized clinical trial shows benefit, there are limitations which require attention and are acknowledged by the researchers.^D The study looked at a notably small sample size of 40 children within a limited age range of 6-12 years and lasted over a period of only 8 weeks.^D These factors alone bring into question the validity of the results, thus requiring further investigation before concrete conclusions can be made. Therefore, though some research points to the potential benefits of Omega 3 supplementation in children with the ADHD diagnosis, it appears that greater bodies of research point to the ineffectiveness or at best, minimal effectiveness of this treatment.

References

A. Kean JD, Sarris J, Scholey A, et al. Reduced inattention and hyperactivity and improved cognition after marine oil extract (PCSO-524^R) supplementation in children and adolescents with clinical and subclinical symptoms of attention-deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled trial. Psychopharmacology. 2017; 234: 403-420.
B. Derbyshire E Do omega-3/6 fatty acids have a therapeutic role in children and young people with ADHD. Journal of Lipids. 2017; 2017: 1-9.

C. Konigs A, Kiliaan AJ. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment. Neuropsychiatric Disease and Treatment. 2016; 12: 1869-1882.
D. Moghaddam MF, Shamekhi M, Rakshani T. Effectiveness of methylphenidate and PUFA for the treatment of patients with ADHD: a double-blinded randomized clinical trial. Electronic Physician. 2017; 9: 4412-4418. Available from: http://www.ephysician.ir. Accessed December 15, 2017.

Healing Properties of Articum Lappa (Burdock Root)?

I recently read a statement on a popular health blog, stating the benefits of Articum Lappa, also known as burdock root. As is the case with many natural supplements, claims for the benefits of Arctium Lappa are extensive. Ranging from a combatant for cancer, a healer for skin and an antibacterial/antimicrobial agent, to an anti-inflammatory substance, a natural diuretic and defense against diabetes, Arctium Lappa is touted as a plant with almost magical properties. From this list of claimed values, the question becomes one of reliability and evidence supporting these advantageous assertions. As always, a little digging provides a clearer understanding of the real story.

In a study aimed at determining the beneficial properties of several plants, researchers attempted to evaluate the antimicrobial activity of the combined plant extracts of artichoke, dandelion and Arctium Lappa. A serial dilution method was employed to assess the antimicrobial activity of this blend when introduced to bacterial strains of Staphylococcus aureus, Escherichia coli, and Salmonella abony. Researchers concluded that using this trifecta of plant extracts proved to be beneficial against Escherichia coli and Salmonella abony but did not show antimicrobial activity when tested with Staphylococcus aureus. Though this study points to the possible benefit of Arctium Lappa  on health, the study has clear limitations for the claims of Arctium Lappa’s sole benefit due to the fact that it was not tested apart from artichoke and dandelion.

In a randomized, double‐blind placebo‐controlled clinical trial, 3 subjects infected with Helicobacter pylori (H.pylori) were studied. Nineteen participants ingested a burdock complex (BC) consisting of burdock (Arctium Lappa), angelica, gromwell and sesame oil and 17 subjects ingested a placebo for a total of eight weeks. Multiple markers were tested, including anti-inflammatory properties, to determine the efficacious nature of BC.  Subjects were evaluated at fourth, eighth, and tenths weeks, with endoscopic examination taking place at the baseline and tenth weeks. Researchers determined that BC significantly inhibited and alleviated inflammatory markers of H-pylori in subjects during the course of the study period.

A study of a key constituents extracted from the seeds of Arctium Lappa, identified as Lappaol F, was performed in regard to its anticancer effects in humans. During the course of the study, researchers investigated Lappaol F and its effect on colon, breast, lung, cervix, and prostate cancers as well as melanoma, osteosarcoma, and leukemia.  Results demonstrated that Lappaol F suppressed cancer cell growth in human cancer cell lines in a variety of tissue types and displayed a time- and dose-dependent relationship.  Researchers stated that Lappaol F offers a novel anticancer constituent, and has the capacity to mediate growth suppression by initiating cell-cycle arrest as well as trigger cell death in some tumor cell lines.

A number of limitations exist in regard to the studies cited. Across studies, the method of plant compound extraction greatly varied, ranging from extraction from seeds to extraction from leaves and stems, suggesting possible differences in quality or potency of the constituents. Some studies used a combination of plants rather than looking solely at the medicinal properties of Arctium Lappa, pulling into question which component was of greatest consequence and whether the effect was due to the pooled benefits of all the components or based solely on one plant.  Further, differing methods of administration were performed, such as ingestion of tea versus consumption via liquid essence form. Another key difference between studies was the method of investigation, ranging from in vitro studies to those involving human participants. In addition, the studies involving human subjects were limited in size and took place over short periods of time. Another limitation is presented in the fact that some studies focused on the benefits of Arctium Lappa as a whole and others used isolated constituents of the plant to test and determine efficacy. All of these factors point to the importance of further investigation into the effectiveness of specific and consistent variables. In other words, examining studies that focus on similar constituents, extraction protocol, testing methods, administration, and observation might provide a better picture of efficacy than studying the varied approaches listed above. However, the purposes of this paper were to present a foundation of possible efficacy for Arctium Lappa, thus presenting the need for further and more detailed research opportunities.

It appears evident that benefit exists in the use of Arctium Lappa for its healing properties, including its anti-microbial, anti-bacterial, anti-inflammatory and anti-cancer effects. Further, varied methods of extraction, administration and components used point to the efficacious potential for this acclaimed medicinal plant. Clearly, as mentioned above, consistency in extraction, test measures and administration should be employed in future research studies to determine specific efficacy but the initial display of benefits is evident following a brief review of the literature.