Robert J. Thiel, Ph.D., N.M.D.
Journal of Orthomolecular Medicine, 2002, 17(1):42-48
  Reprinted with the permission of the Journal of Orthomolecular Medicine


Background: Children with Down syndrome tend to be short. There is no known effective medical intervention to address height for these children. Since 1986, Dr. F. Jack Warner has specialized in seeing people with Down syndrome. Warner uses an unconventional protocol which includes interventions such as nutrition (HAP Caps, flaxseed oil, N, N-dimethylglycine), physical therapy, ophthalmology, and conventional medicine. Warner claims his interventions can help make children with Down syndrome more like non-Down's children. The purpose of this investigation was to determine if the Warner protocol improve growth for children with Down syndrome.
Method: This investigation used a pretest-posttest, natural control group design. An independent investigation of a random sample of Warner's records was performed. Height and weight data, based on age, were compared against growth grids for Down's children for two visits to the Warner House: the initial measurement and the final measurement.
Results: An analysis of the sample suggests that the combined interventions appear to significantly improve height (p <.001) for children with Down syndrome. The average (mean) height percentile grew from 63.4 to 76.0 (gender was not a significant factor). Although weight percentile went from 52.2 to 56.2 (p=.209), there was a significant difference in gender with the male percentile increasing from 45.2 to 53.7 (p=.035), while female percentile decreased from 60.9 to 59.3 (p=.755).
Conclusion: Nutrition is the most likely intervention to be credited for improving height. A prospective study to test this position should be performed.


Trisomy 21, more commonly referred to as Down syndrome, is a genetic disorder which is present in approximately 1 out of every 700 live births. Although there is a consensus that Down syndrome is caused by total or partial triplication of the 21st chromosome, the underlying causes that interfere with normal chromosomal duplication are a matter of some dispute [1]. While there is no recognized effective medical intervention for trisomy 21, there are treatments for complications such as cardiovascular disorders, hypothyroidism, and infections [2]. Although some physicians and a few scientists are now recommending a variety of nutritional interventions as part of a treatment program for those with trisomy disorders, the prevalent medical opinion appears to be that nutrition is ineffective [3,4].

One of the well documented characteristics of Down syndrome is impaired growth. Down's patients tend to be short [5]. At age 18 the median average female with Down Syndrome grows to approximately 4'9½", whereas the average male grows to approximately 5'½" [6].

Since 1986, Dr. F. Jack Warner (MD) has specialized in seeing non-institutionalized patients with trisomy 21. He is associated with the Warner House, a non-profit organization for the study and treatment of trisomy disorders. The Warner House uses a multi-disciplinary approach with interventions including nutrition, medicine, physical therapy, and opthamology. Dr. Warner has seen thousands of patients who suffer from trisomy disorders, but because many of these patients are seen only at traveling clinics, follow-up records do not exist on all the patients. All Warner House patients, or their legal guardians, sign a consent form allowing data to be included in published reports.

Although Dr. Warner has presented oral and written information on these interventions to a variety of organizations which deal with trisomy disorders [i.e. 7,8], he has not published any peer-review articles in recent years. This has been a basis for criticism of Dr. Warner's work: "There have been no structured studies of the effects of 'HAP Caps'. Warner claims that records on 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" [4]. This investigation is intended to determine if the Warner interventions might have any efficacy on growth and to determine if further research would be warranted.


The nutritional interventions used by Warner House are a combination of a multiple vitamin/mineral formula called "HAP Caps" (HAP stands for Health and Progress), plus flaxseed oil (1-3 teaspoons normally recommended), N,N-dimethylglycine (an amino acid derivative, with 30-500 mg normally recommended), and sometimes other nutritional substances. Each HAP Caps capsule contains beta carotene 2000 I.U., vitamin B-1 6.25 mg, vitamin B-2 6.25 mg, vitamin B-3 6.25 mg, calcium pantothenate 25 mg, vitamin B-6 6.25 mg, vitamin B-12 1.25 mcg, vitamin C 100 mg, vitamin D-3 33 I.U., biotin 25 mcg, vitamin E 33 I.U., choline 50 mg, folic acid 50 mcg, inositol 5 mg, PABA 75 mcg, cobalt 5 mcg, iron 5 mg, manganese 125 mcg, copper 40 mcg, molybdenum 75 mcg, selenium 7.5 mcg, zinc 2.5 mg, organic iodine (from kelp) 18.75 mcg, rutin (a bioflavonoid) 25 mcg, quercitin (a bioflavonoid) 6 mg, liver extract (bovine) 6.25 mg, betaine hydrochloride 1.8 mg, ox bile 3.6 mg, pancreatin (supplies enzymes) 2.8 mg, co-enzyme Q10 8 mg, and the amino acids glutamine 75 mg, taurine 4 mg, and tyrosine 55 mg--the number of capsules recommended varies by patient weight [8] and normally ranges from 2-12 per day (approximately 1 HAP Cap per 10 lbs.). HAP Caps have a similar composition to the 'U' series nutrients that Dr. Turkel pioneered decades previously (which Turkel safely used for many children with Down syndrome [3]). The Warner House recommends physical therapy for all trisomy patients. It also advises that all with trisomy 21 disorders avoid cow's milk products. Ophthamological interventions, interventions for infections, thyroid medications, and other conventional medical interventions are recommended when indicated.


At Warner House, height and weight data is initially recorded from a medical scale (containing a height attachment) by a trained nurse; follow-up data is normally provided by the same nurse or sometimes is provided by the parents. This specific investigation used a pretest-posttest, natural control group design. Height and weight data (in Warner files), based on age, were compared against growth grids for Down's children [6] for two visits to the Warner House: the initial measurement and the final measurement (the last measurement in the files). "Because of the short stature and abnormal growth pattern in children with Down syndrome, it is preferable to use the growth grids developed specifically for this disorder to evaluate the child's stature" [6]. Those grids are based on actual non-institutionalized children with Down syndrome, thus serve as a natural control group for this investigation.

Warner made all of his non-archived files available. Files were randomly selected using a random number table. Files were accepted if they had initial and final age, combined with an initial and final measurement of height and/or weight. Files for patients with ages above 16.0 were excluded. Of the selected files, 84 met the criteria for age and height and 90 met the criteria for age and weight. Approximately 1,500 non-archived records were estimated to be available which met these criteria.

This investigation was pre-approved by an independent review board.


84 of the records selected contained before-and-after height and age information as shown in Table 1.

Table 1 Height
Gender    N    Attribute  Initial Mean Final Mean
 Attribute as Percentile on Down's Grid 
Female 36 Height 63.1% 73.6%
Male 48 Height 63.6% 77.8%
Total 84 Height 63.4% 76.0%

The total data was analyzed utilizing a paired T-test. With a 95% confidence level the mean difference of improvement is 6.3% to 18.9%; T-value 3.99; p-value <.001. Gender differences were not statistically significant. The average (mean) age at the initial appointment was 2.2 years (range 1 week to 10.2 years) whereas the average age at the final appointment was 5.3 years (range 6 months to 16.0 years).

90 of the records selected contained before-and-after weight and age information as shown in Table 2.

Table 2 Weight
Gender    N    Attribute  Initial Mean Final Mean
 Attribute as Percentile on Down's Grid 
Female 40 Weight 60.9% 59.3%
Male 50 Weight 45.2% 53.7%
Total 90 Weight 52.2% 56.2%

The total data was analyzed utilizing a paired T-test. With a 95% confidence level the mean difference of improvement is -2.3% to 10.3%; T-value 1.27; p-value =.209. In contrast to height data, gender differences in weight appeared to be significant—the males significantly increased (p=.035), whereas the females slightly decreased (though the decrease was not statistically significant, p=75.5). The average (mean) age at the initial appointment was 2.3 years (range 1 week to 10.5 years) whereas the average age at the final appointment was 5.3 years (range 6 months to 16.0 years).


The advocacy of an interdisciplinary approach for Down syndrome patients predates Dr. Warner's involvement [9]. The fact that children undergoing the Warner protocol showed significant improvement in height using age-adjusted Down's grids seems to suggest that interventions such as those used by Warner are helpful when begun at an early age. Of various measures, "the measure of growth and body composition in the child, is the most objective indicator of that child's nutritional status" [10].

It is of interest to note that the height percentile of the average child in this study was began at 63.4. If normal growth patterns were to be expected to occur, from a statistical point of view, the height for these children should have tended downwards (towards the 50th percentile). Instead, these children grew. As the upper border on growth (100.0-63.4) was smaller than the lower border on growth (63.4-0.0), this makes the results of this investigation of even greater interest. While this investigation does not prove that growth of children with Down's syndrome will always improve under the Warner protocol, it does show that most of those who followed it for at least some period did grow beyond what would normally have been expected.

The weight results were somewhat unusual. The average female weight percentile dropped from 60.9 to 59.3 (statistically insignificant), while the average male weight percentile increased from 45.2 to 53.7 (statistically significant). While Warner's records do not contain any body mass index calculations, since the growth in height exceeded the growth (or reduction in the case of the female subjects) in weight, it is reasonable to conclude that the average BMI probably reduced. The initial mean age for males (2.1 years) and females (2.5 years) was fairly close as was the final mean age for males (5.1 years) and females (5.6 years), thus weight changes are not explained simply by age differences between the sexes.

The use of nutrition for persons with Down syndrome has been repeatedly challenged [4,11,12], yet there is evidence in the literature that supports that portions of the interventions provided by the Warner House may have some affect on those with trisomy 21. Even some mainstream researchers have recommended vitamin and mineral supplementation for those with Down syndrome [13,14], but they have not apparently involved growth data. There have been some reports of height and weight based upon diet [i.e. 15], for Down's children, however, and some ongoing research involving growth hormone (GH) [16].

It has been speculated that thyroid abnormalities may increase the risk of developing dementia [17] (Down's patients often develop an Alzheimer's like dementia as they age [2]). Down syndrome patients have increased incident of thyroid disorders [1,18,19], thus thyroid medications, as recommended by the Warner House, would be expected to have at least some symptomatic improvement [20] (though this investigation did not measure symptomatic improvement). Other researchers have concluded that thyroid medications, when confirmed by testing, do help reduce problems faced by those Down syndrome patients [21] and even that "It would seem evident that Down syndrome individuals with hypothyroid disease benefit significantly from thyroid replacement therapy" [22]. The primary thyroid hormone (T1) is composed of iodine and tyrosine [23] and since some Down syndrome patients appear to have difficulties converting phenylalanine into tyrosine [24], it appears logical that supplemental tyrosine may help these patients. Warner's protocol does include iodine which has been shown to be helpful for some thyroid problems [25] and the amino acid tyrosine.

Warner's protocol also includes the mineral zinc. Down syndrome patients often have below normal plasma levels of zinc [26,27]. Supplementation with zinc has been shown to increase DNA synthesis in Down's patients with low zinc levels [28]. Since one study found that zinc reduced TSH by 34% for hypothyroid Down syndrome patients [29], it is possible that the supplemental zinc may also positively affect some Down's patients [30]. It has been speculated that zinc deficiency may be a cause of subclinical hypothyroidism in Down's syndrome children [29]. Low iodine levels, as well as low zinc levels, can sometimes be associated with short stature [25,31]. A study involving supplemental zinc for stunted infants concluded that it can increase growth rate to that of non-stunted infants [32]. In addition, it has been found that children with Down syndrome become deficient in a zinc-containing insulin-like growth factor type 1 (IGF-1) after one year of age [33]. Not only has supplementation with zinc been shown to increase IGF-1, one study found that zinc supplementation increased growth in 15 of 22 children with Down syndrome [33].

Triplication of the 21st chromosome causes metabolic disturbances which lead to an accumulation of various metabolic precursors and a deficiency of certain end products--this is one of the basic reasons why nutritional interventions make scientific sense for persons with Down syndrome [3]. Superoxide dismutase and alpha and beta-interferon levels are elevated [2,34] (interestingly people who live past 100 appear to have lower levels of superoxide dismutase than the general elderly population [35]). It is of interest to note that even though zinc is a constituent in cytoplasmic superoxide dismutase, zinc supplementation has been found to reduce superoxide dismutase levels in non-Down syndrome female subjects [36]; it has been hypothesized that supplemental vitamin E may reduce superoxide dismutase-generated oxidative damage in Down syndrome patients [37]. Levels of alanine, cysteine, isoleucine, lysine, phenylalanine, and threonine seem to be elevated, yet tyrosine, folate, manganese, iron, thiamin, vitamin B12, vitamin C, vitamin E, and selenium levels appear to depressed (additional nutrients have also been implicated) [3,24,26,38,39]. Some minerals, such as calcium and magnesium, seem to be higher than non-Down's patients in some areas of the body, yet lower in others areas [3,24]. Selenium itself affects thyroid metabolism [40], it is possible that supplementing with it may have some benefit. Long-chain omega-6 polyunsaturated fatty acid concentrations appear to be higher in Down syndrome patients [41]. Down syndrome patients have an additional copy of the gene that codes for cystathione synthase, which greater increases production of that enzyme and results in lower levels of homocysteine than others have, as well as lower incidence of atherosclerosis [42]. Folate metabolism affects homocysteine production and supplementation with folate is being investigated to see if it may help normalize height in infants with Down syndrome [43]; supplementation with a combination of nutritional antioxidants to help normalize height is also being investigated [43]. It has been speculated that the alteration of the conjunctival epithelium in patients with Down syndrome may be due to altered metabolism of vitamin A [44]; a study involving young, non-Down's children found that supplemental vitamin A improved the linear growth of children with very low serum retinol levels [45]. Disorders of vitamin D metabolism have also been speculated for Down's patients [3,46], and since vitamin D does affect bone development, it does play a role in height [47].

Down's patients are more susceptible to certain ophthalmological problems than the general public (most notably strabismus) which leads to distortion of vision [48]. Early ophthamological interventions, such as provided by Warner House, could be expected to lead to improved vision. It does not seem likely, though, that this would affect height or weight.

Physical therapy, such as recommended by Warner House, could be expected to improve muscle tone, which this study did not assess. Some reports suggest that physical therapy could have some effects on appearance and intelligence of those with Down syndrome, especially when used as part of a multidisciplinary approach [49-50], but no controlled studies on height have been found.

It should be noted that Warner is not the only health professional involved with trisomy 21 to advocate an interdisciplinary approach, with the resultant combined protocols, to best benefit Down's patients. Others, while not necessarily advocating nutrition, feel that an interdisciplinary approach is likely to be of the most benefit to Down's patients [51].


Although this investigation was preliminary, it appears that there is some efficacy in the Warner protocol regarding height. As the Warner protocol combines nutrition with physical therapy, medicine, and ophthalmology, it is not possible to statistically segregate the impact of any one of those interventions. It is possible that all of the interventions may work synergistically to improve height or that one or more interventions on its own has the most (or the entire) effect. There is at least some supporting evidence in the literature for nutrition being able to influence growth. A prospective study would be needed in order to assess the possible impact of any single intervention. This investigator believes that the data in this paper favorably support the need for such a study.


The investigator wishes to thank Steve Rein, Ph.D., Statistics Department, California Polytechnic State University, San Luis Obispo for his assistance in this project.


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