MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

nemoci-sympt/METABOLISMUS/downuv-syndrom/80-bez-efektu

5-hydroxytryptophan


AMK

  • 1992 by Jerome Lejeune, M.D. reported a consistent deficiency of serine and excess of cysteine and lysine
  • Postulated that the supplemental amino acids balanced the blood levels, making the biochemical workings of the body normal
    • However, a subsequent study of 22 children found no such abnormalities in serum or urinary amino acid levels
  • Amino acid supplements can cause an unpleasant odor in the user’s urine and sweat.
  • quackwatch.org/11ind/down/

Alpha-lipoic acid, ascorbic acid, and alpha-tocopherol

Randomized, double-blind, placebo-controlled trial over a 2-year period daily antioxidant supplementation

  • Alpha-lipoic acid, ascorbic acid, and alpha-tocopherol in subjects with DS and dementia
  • Long-term supplementation with these antioxidants is safe
  • Treatment did not improve cognitive function nor prevent cognitive decline in individuals with DS
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC7464577/

VITAMIN B6 / 5-HYDROXYTRYPTAMINE(5-HTP) SUPPLEMENTATIONI in DS


Choline

  • As children with Down syndrome age, there is a loss of neurons that produce the neurotransmitter acetylcholine
  • It is presumed that this loss may cause difficulties with memory and cognitive function.
  • Choline is promoted for increasing myelinization of neurons and for increasing levels of the neurotransmitter acetylcholine.
  • However, there is no evidence that oral choline supplements do either of these things in people with Down syndrome.
  • Zřejmě je pokles paměti způsoben něčím jiným než deficitem cholinu.
  • quackwatch.org/11ind/down/

Docosahexaenoic acid (DHA)

  • Omega-3 fatty acid is an important constituent of cell membranes
    • Especially in the retina and brain
  • DHA is synthesized in the body from other fatty acids in the diet
  • Studies have indicated that premature infants may not be able to synthesize enough on their own
    • So infant formulas for premature babies should be fortified with DHA
  • Breast milk contains DHA
    • The World Health Organization and several other organizations have asked the FDA to include it in regular infant formulas in the US
    • (DHA is already a component in infant formula in several European countries.)
  • Promoters of DHA for older children with Down syndrome
    • Claim that its use will improve eye and neurologic development
    • No research indicates that children with Down syndrome lack DHA, cannot make enough, or can benefit from DHA supplements.
  • Studies have shown that the critical period for supplementing DHA in preterm infants is the first two months of life
    • Little benefit beyond that should be expected
  • Promotion of the use of other fatty acids has no proven benefit for children with Down syndrome
  • Use of DHA entails some risks
    • Too much can actually suppress the immune system, which is already impaired in people with Down syndrome
  • Souhlasím s tím, že samotná DHA je asi nesmysl, smysl ale má olej z celých ryb a ještě konzervovaných v olivovém oleji
    • Po suplementaci rybím tukem jsem viděla metální zlpšení u vlastních dětí na vlastní oči a dělo se to i ve věku kolem 1 roku, kdy začínaly mluvit, takže nesouhlasím s tak příliš skeptickým tvrzením - deficit, který je častý i u normálních dětí - je rozhodně velké mínus bez ohledu na existenci či neexistenci DS
  • Samotné DHA však snadno podlehne oxidaci, takže při zvýšeném ox. stresu může být i nevýhodou a zhoršit stav (např. u ALS, kd emůže být také zvášená SOD aktivita)

DMSO (dimethyl sulfoxide)

  • The Sierra Clinic, located in Mexico, is treating children with muscular injections of amino acids and DMSO
    • In an attempt to improve cognition and motor skills
  • One study supports such use
    • But the study was not blinded
    • Has not been confirmed by any other researcher
  • One study on oral DMSO in children with Down syndrome found no benefit
  • quackwatch.org/11ind/down/

Donezepil hydrachloride

“Evaluating The Safety Of Donepezil Hydrochloride (Aricept)

  • For Up To 1 Year In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome—Follow-Up To A 10-Week, Double-Blind,

Placebo-Controlled Trial”

“Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (Aricept) In The Treatment Of The Cognitive Dysfunction

“Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (Aricept)

  • Donepezil Hydrochloride (Aricept) For Up To 1 Year In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome
    • Follow-Up To A 10-Week, Double-Blind, Placebo-Controlled Trial
  • NCT00675025
  • Terminated (Sufficient evidence of efficacy not met. Discontinuation not based on any safety concerns.)
  • First Posted : May 8, 2008
  • Results First Posted : March 29, 2021
  • clinicaltrials.gov/ct2/show/NCT00675025

Heller et al. [56] have reported an open-label case series of six non-demented adults subjects with DS (aged 20–41 years) receiving 5 then 10 mg donepezil over 24 weeks. Despite transient side-effects expectable from cholinergic overstimulation, all subjects tolerated well the 10 mg dosage. A small but significant improvement (p < 0.05) in expressive language was observed at 24 weeks in four sub-tests of the Clinical Evaluation of Language Function-Revised (CELF-R). However, the small sample of subjects and the lack of a control group render the outcome of this experiment difficult to interpret.

Heller et al. [57] reported results from a 16-week pilot clinical trial on the effects of donepezil on the language of 5 children with DS aged 8 to 13 years. The drug was dosed orally at 2.5 mg once daily for 8 weeks and at 5 mg for the remaining 8 weeks. Two language measures were used: the Test of Problem Solving (TOPS) and the Clinical Evaluation of Language Fundamentals (CELF-3). Medication effects were measured by changes from the baseline to performance at weeks 8 and 16. No subject experienced serious adverse effects from the administration of the medication. T-tests yielded no significant indication of change in language performance between base line and TOPS scores at 8 and 16 weeks. However, a significant improvement (p < 0.003) was registered in the mean CELF-3 performance from baseline to week 16. Results from this study are also difficult to interpret owing to the lack of a control group and the small sample of subjects.
Kishnani et al. [58] tested the efficiency of donepezil in a sample of 123 young adults with DS (aged 18–35 years), who had no evidence of AD, in a 12-week randomized, double-blind, and placebo-controlled study. Experimental subjects were treated with doses of 5 mg per kilo of weight for 6 weeks and then 10 mg/kilo in the following 6 weeks. Cognitive measures included the Severe Impairment Battery (SIB), the Rivermead Behavioral Memory Test for Children, and the Clinical Evaluation of Language Fundamentals (CELF-3). Additionally the Vineland Adaptive Behavior Scales were administered. Donepezil appeared safe. However, two subjects had to be withdrawn from the double-blind phase for hypertension rated as possibly problematic by the investigators. Outcomes suggested efficacy of the drug in some but not all subjects, which the authors estimate consistent with the phenotypical variability in DS. However, improvements were also observed in the placebo group, particularly on the SIB, during the double-blind phase of the study, preventing clear-cut conclusions regarding the cognitive specificity of this molecule.
Kishnani et al. [59] assessed the efficiency and safety of donepezil with 129 children and adolescents with DS (aged 10–17 years) in a 10-week, randomized, double-blind, placebo-controlled, and multicenter study. Participants received a dose of 2.5 mg/kilo donepezil in the first part of the experiment, increased every 14 days until reaching 10 mg/kilo. Measures included the Vineland-II Adaptive Behavior Scales Parent/Caregiver Rating Form (VABS II/PCRF). The medication appeared to be well tolerated. During the double-blind phase, the VABS II/PCRF scores improved significantly (p < 0.001) in both the treated and control groups but with no significant difference between groups.

HAP CAPS

  • A derivative of Turkel's "U series" (called "HAP CAPS")
  • Developed during the 1980s
  • Currently promoted by Dr. Jack Warner and colleagues through "The Warner Clinic"
  • Contains a variety of vitamins and minerals
  • no structured studies of the effects of "HAP CAPS"
  • Warner claims that records on the 4,200 'patients' who have received "HAP CAPS" are kept
    • Yet admits that no attempt has been made to analyze them in any systematic way
  • Neither have these records been made available for others to analyze
  • At a recent presentation by Warner and colleagues in London, the few medical professionals in the audience voiced considerable criticism of Warner's claims
    • Pointing out that evidence was required
    • Some 'results' were exceedingly unlikely to have been influenced by the formulation
  • library.down-syndrome.org/en-us/news-update/01/2/multinutrient-formulas-other-substances-therapies-down-syndrome-overview/

Piracetam

  • Piracetam increases brain oxygenation and improves GABA neurotransmission. Lobaugh et al. [70] assessed the cognitive and adaptive effects of piracetam in a double-blind study with 18 children with DS (aged 7–13 years). The experimental group received 80–100 mg/kg piracetam per day for 15 weeks. No statistically significant benefit was observed in the treated sujects in comparison with the control group in a series of tests measuring learning, attention, and memory, as well as on the adaptive scales. Treatment induced side effects of irritability and poor sleep in 7 subjects.
  • www.aimspress.com/article/doi/10.3934/Neuroscience.2020012?viewType=HTML

Rivastigmine

Study in Adolescents With Down Syndrome (DS-Riv)”

“Efficacy of Rivastigmine in Patients With Down Syndrome”

20-week double-blind, placebo-controlled trial

  • Safety and efficacy of rivastigmine in 22 children and adolescents with DS aged 10-17 years
  • No group differences were found on safety measures
  • Results did not demonstrate evidence for significant improvement in aspects of cognition, language, or overall function in the children receiving rivastigmine
  • Safe and well-tolerated for children and adolescents with DS
    • But may not be effective for improving performance
  • [2016 Wiley Periodicals, Inc.]
  • pubmed.ncbi.nlm.nih.gov/27061338/

Randomized, double-blind, placebo-controlled, crossover design, 12-month trial

  • Rivastigmine and placebo in different order for 6 months
  • Neuropsychological assessment including Vineland Adaptive Behavior Scales and NEPSY will be evaluated before and after medication
  • www.clinicaltrials.gov/ct2/show/NCT00748007
  • Rivastigmine was tested by Heller and associates [60],[61] in two open-label studies with 10 children and adolescents with DS (8 boys and 2 girls) aged 10 to 17 years. Doses at the beginning of the intervention were 1.5 mg/kilo increased to 3 mg/kilo and 4.5 mg/kilo in the following weeks. Five subjects reported no adverse events with the medication, but five others signalled transient vomiting, diarrhea, fatigue, or insomnia related to cholinergic enhancement. After 16 weeks, there were statistically significant gains in expressive language on the Test of Verbal Expression and Reasoning (TOVER; p < 0.02), as well as for language measures (narrative memory and immediate memory for names on the Developmental Neuropsychological Assessment Test (NEPSY; p < 0.02). There were also significant improvements in attention on the Leiter-R Attention Sustained Tests A and B (p < 0.01 and p < 0.02, respectively). Five participants (4 boys and 1 girl) continued the treatment for another 38 months. Longer-term use of rivastigmine appeared to have no adverse effect on overall health. A comparison of median performance change between those who continued the treatment for 38 months versus those who did not yielded no statistically significant difference. However, two subjects demonstrated important improvements in adaptive function (measured on the VABS) over the longer-term period with continued rivastigmine administration.

Turkel's formula

  • Added the drug piracetam (Pure Nootropics, Albuquerque, New Mexico)
  • None of these products, however, have been proven to be effective
  • Policy statements by patient advocacy groups and professional organizations have clearly declined to support supplement use for individuals with Down syndrome because of the lack of proven benefit and safety
  • www.jpeds.com/article/S0022-3476(18)30735-2/fulltext [2018]


U series of drugs and supplements

Bumbalo and coworkers double-blind randomised controlled trial

  • ‘U series of drugs’ on 24 children with DS aged 3 months to 11 years
  • Reported no significant treatment effects after 1 year
  • ‘U series of drugs’ was developed by Henry Turkel - popular therapy for DS in many countries
  • Supple-ment contained 48 items which, in addition to vitamins andminerals, included substances such as:
    • Rutin,
    • Naphazolin hydrochloride
    • Propyl paraben
    • Pentylene tetrazole
  • Notheoretical rationale was given for most of the items includedin this supplement.
  • onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-8749.2000.tb00072.x



Vasopressin

  • Enhances learning inanimals

Eisenberg and colleagues treated 9 individuals with DS, aged 10 to 42 years

Vitamin E

“Vitamin E in Aging Persons With Down Syndrome”

“Multicenter Vitamin E Trial in Aging Persons With Down Syndrome”

Vitaminoteraphy


TARGETED NUTRITIONAL INTERVENTION (TNI) SUPPLEMENTATION

  • Probably the most popular nutritional therapy currently advocated for DS
  • ‘target’ DS abnormalities
  • Typical TNI supplement contains about 56 nutrients including
    • Vitamins,
    • Minerals,
    • Enzymes,
    • Amino acids,
    • Electrolytes etc.
  • Unfortunately - no published trial on the safety or efficacy of this supplement
  • Typical TNI preparation contains
    • 1000 mg of vitamin C - which may be unsafe in children
      • Daily intake of 500 mg of vitamin C has been shown to have prooxidant effects in adults
  • onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-8749.2000.tb00072.x

MEGAVITAMIN/MINERAL SUPPLEMENTATION

Randomised 22 children aged 5 to 15 years with learning disability (five of whom had DS)

  • 1981, Harrell and colleagues
  • To receive either a megavitamin/mineral preparation or placebo for 4 months initially
  • After the first phase, all the par-ticipants received the megavitamin/mineral supplement foranother 4 months
  • Supplement consisted of 11 vitamins and eight minerals in high doses
  • Investigators reported dramatic improvements in
    • IQ,
    • Growth,
    • Physical appearance,
    • Language,
    • Educational attainment
    • General health of the treated participants
  • Thisstudy had significant problems in that the loss of participants reduced the already small sample from 22 to 16
    • Only fourof these had DS
  • Findings stimulated several more trials of megavitamin/mineral supplementation

Six randomised controlled trials attempted to replicate the findings


Vitamíny

  • In a double-blind study, 24 Down syndrome children, ages 6 to 17 years living at home
  • Megadose multi-vitamin/mineral supplement for 4 months.
  • A matched group of 23 children received a placebo in identical form.
  • Children's IQ, vision, and visual-motor integration were tested before and after supplementation, and weekly checks
    • No differences were found on any measures as a result of supplementation.
  • pubmed.ncbi.nlm.nih.gov/6227244/

O úroveň výše

Poslední aktualizace: 30. 9. 2024 22:16:54