Why we urgently need new studies on TNI

During my pregnancy with my daughter, I encountered Targeted Nutritional Intervention (TNI) within days of her diagnosis of with Down Syndrome. After I was initially full of skepticism, as a natural scientist I started looking for scientific articles on the treatment of Down syndrome - and found what I was looking for: "Prenatal treatment of Down syndrome - a reality?" (Guedj F., 2014). This article was published just a few weeks before my diagnosis and convinced me to start TNI.

I found other articles suggesting that Down Syndrome as a metabolic disease is treatable - the sooner the better (Stagni F., 2015). As a biologist and geneticist, it seemed logical to me that the disease is not just a "syndrome", but the result of the extra chromosome and the additional genes on chromosome 21. The fact that Down syndrome is a neurodegenerative disease surprised me at first, on the one hand it scared me, on the other hand it motivated me to do everything I could to ensure that my daughter was developing well.

Danica Donelly Photography

With the scientific articles I had collected, I went to the Down Syndrome special consultation at our children's hospital in Minneapolis, Minnesota (USA) - I was excited to talk to the experts. When I asked at the time how the clinic felt about the treatment of Down syndrome with dietary supplements or TNI, I got the following answer: "We can't recommend anything because there are not enough studies". I still remember my reaction well: I was confused, surprised, disappointed - as I had a stack of articles in my hand. I left the office in frustration and never went back.

This feeling of frustration and disappointment stayed with me for a long time. It didn't matter if we were talking to the neurologist after the lack of oxygen during birth, who insisted that there was no possibility of neurogenesis. Or discussing with endocrinologists whether our daughter was just small or actually had a growth hormone deficiency. Or the pediatrician and the cardiologists who claimed that TNI does not make sense, but on the other hand kept telling us: "Keep doing whatever you're doing". Even if there were supposedly not sufficient studies, they always remarked on how amazingly well our daughter developed.

The unpleasant taste of frustration has stayed with me to this day. I hear daily from many of my families in my practice that they have to fight for every blood draw, many doctors refuse to take blood at all and to check values ​​that are necessary for individual treatment with TNI. The major Down Syndrome organizations worldwide speak out against dietary supplements. A report from the Netherlands comes to exactly this conclusion: "The scientific evidence is insufficient, dietary supplements should not be recommended for improving health and cognition in Down Syndrome." (van der Haar, 2021). This article is now being used by Down Syndrome organizations in Germany to continue to speak out against TNI.

Since the feeling of frustration has spread again within me, I would like to point out some weaknesses of the report. The study (which is not a peer-reviewed article) consists of a survey among parents (243 families took part) and a literature review. In addition, five parents of a child with Down syndrome and five experts were questioned in interviews on the subject. The article was written by two nutrition scientists from the Netherlands. The literature review cites many good articles, and the parent survey revealed a high proportion of parents giving their children nutritional supplements (61%). The focus is on the one hand on the question of nutrient deficiencies in children with Down syndrome (zinc, vitamin A, B12, D, folate, iron) and on the other hand on the question of scientific evidence of the positive effects of supplementation. The experts and nutritionists surveyed were all critical of supplementation - pointing out that nutrient deficiencies should primarily be compensated for by diet.

Claim 1 - Dietary supplements should only be used if there a deficiency is detected

My practice also focuses on healthy nutrition and the function of our microbiome. There is little point in giving supplements without understanding the importance of healthy eating. Nutrients can only be absorbed by the intestine if the intestinal mucosa is healthy - regardless of whether they are components of food or supplements. Unfortunately, to date, the German guideline does not recommend testing for zinc, ferritin, or any other mineral, although deficiencies are common even in the general population. Vitamin D is also not included and is only routinely tested by some doctors. In the Netherlands, vitamin D is recommended up to the age of 4, in Germany only up to the age of 2. It is incomprehensible why a deficiency wouldn't arise later in life in our latitudes. Vitamin D is an important hormone with a number of functions in the body. Very few of my patients have adequate vitamin D levels. Vitamin D supplements cannot only be dosed according to weight and age - in addition to the lack of co-factors (e.g. magnesium, vitamin K), genetic factors play a role (mutations in the vitamin D receptor, VDR), as well as liver function (which is important in Down syndrome due to lack of glutathione and very often restricted). Since vitamin D is fundamentally important for the function of our immune system and children with Down syndrome are known to have immune dysfunction, the importance of vitamin D and checking individual levels could have been emphasized here.

Claim 2 - A one-size-fits-all advice is not possible and micronutrient status should be assessed individually

Even if the basic TNI protocol is initially the same for all people with Down syndrome, it should always be individually adapted. These include the different requirements for fat-soluble vitamins (A, D, E), B vitamins (B6, B9, B12) and methylation (CBS and MTHFR mutations), neurotransmitters (histamine, serotonin, acetylcholine), and the reduction of oxidative stress and chronic inflammation. Some children are protected by their individual genetics, therefore require fewer nutrients or can compensate for part through diet. For this reason, International Nutrition (Nutrivene) recommends checking various laboratory parameters 6-12 months after the start of TNI. International Nutrition is a compound pharmacy, which is why we can adapt the Nutrivene Daily supplement individually for patients. Without lycopene (because the child does not accept the red color), without vitamin C (because the stomach is sensitive) or with less vitamin A, B6, B12 or E (because the need is lower). As a therapist and scientist, I spend a lot of time optimizing the TNI protocol for my patients. This is anything but easy, every patient is a complex puzzle and the missing pieces are not always easy to find. The risk of overdosing with TNI is low with the appropriate controls and adjustments.

Lack of understanding why we use TNI

The authors misunderstand the goal of TNI and focus on addressing nutrient deficiencies. However, we only use TNI to a very small extent to compensate for the lack of nutrients. TNI is much more important for specifically inhibiting the extra genes of chromosome 21. This is the only way to regulate the misguided biochemistry and avoid consequential damage. Unfortunately, this area is not mentioned at all in the article, although the name TNI indicates exactly this (targeted). We use various nutraceuticals that are well documented in scientific research. The article only discusses EGCG, a component of green tea extract that affects the DYRK1A gene.

Among others, the following are missing:

Curcumin (APP), Resveratrol (miRNA155), Lycopene (RCAN1), Apigenin (CBS), Luteolin (miRNA132).

The article lacks any understanding of what we actually want to achieve with TNI: reduction or normalization of the increased amount of free radicals (oxidative stress) and thus prevention of neurodegeneration and premature aging, support of neurogenesis via BDNF, reduction of chronic inflammation and thus prevention of early Alzheimer's dementia (oxidative stress and inflammation act synergistically), balancing several neurotransmitters (serotonin, acetylcholine, histamine), supporting healthy sleep phases for detoxification of the brain via the glymphatic system, promoting normal mitochondrial function and regeneration, etc. I could go on for hours on here why TNI is so important to our children.

Single supplements or a combination of fewer substances (Ellis Trial, 2008) cannot be sufficient to balance out an entire chromosome (even though chromosome 21 is the smallest in our body cells). Any scientific study that does not understand the complexities of genetics and epigenetics, the intertwined connections between genes, biochemical pathways, nutrients and organ function, of Down Syndrome will have difficulty finding a positive effect on cognition. It is the combination of ALL factors that is decisive for the cognitive development of people with Down syndrome over years or decades.

Zinc and thyroid function in children with Down syndrome

Thyroid dysfunction is very common in children with Down syndrome. An increased TSH value is common (regulatory factor of the brain to the thyroid gland), with initially normal values ​​of the free hormones T3 and T4. It has been known since the 1970s that zinc can support the thyroid function in children with Down syndrome and thus also growth. However, if you only limit yourself to zinc in the complex function of the thyroid gland, you will see few positive effects in studies. The thyroid gland is sensitive to any kind of "stress" - this includes increased levels of oxidative stress, chronic inflammation and the development of autoimmune diseases (e.g. celiac disease), infections, lack of vitamin D, iron, B vitamins, iodine and selenium. Since these values ​​are rarely examined routinely, statements about the function of the thyroid gland are difficult. The TNI program supports the thyroid gland holistically at all levels, which is why improvements in values ​​are almost always seen with TNI treatment.

Claim - 3 Children with DS in the Netherlands are unlikely to suffer from nutritional deficiencies caused by celiac disease because this [celiac] is detected early

It has long been known that the development of the autoimmune disease celiac disease takes several years, which is why the antibody screen in the German guideline is only recommended from the age of 3. However, by the time antibodies can be detected in the children's blood, nutrient deficiencies can long have occurred. I therefore generally recommend checking the laboratory values ​​for zinc, copper and iron, as well as a comprehensive screen for antibodies and a DNA analysis of the HLA-DQ status. If zinc levels are not improving despite TNI, if there is a lack of iron despite a diet rich in iron, if a child is not growing sufficiently despite TNI - then a comprehensive screening for celiac disease should be carried out.

Claim 4 - The respondents to our survey were predominantly highly educated women. In this respect, the sample was not representative

In my experience as a therapist and mother, it is actually mostly the mothers who find their way to TNI, who are active in the Facebook groups, who come to the appointments at my practice, who prepare supplements for their children. This is not to say that fathers are less interested in helping their children, or that fathers are generally more opposed to TNI and supplementation. In our society, however, it is still the case today that most mothers stay at home with the children and fathers work full-time - in my opinion the survey is therefore quite representative.

Claim 5 - Different viewpoints on the use of dietary supplements were taken into consideration; motivations and opinions of parents, doctors, dieticians and a manufacturer of dietary supplements. We obtained a complete picture of the topic

I find it more than questionable to describe a survey of 243 families in the Netherlands and interviews with five pairs of parents and experts as a "complete picture". TNI is used in almost every country worldwide. In Germany and the surrounding countries alone, I have treated well over 400 patients with Down syndrome since June 2019 and have been able to collect an extensive amount of data and experience.

The above report with its mentioned vulnerabilities will again lead to doctors around the world advising against TNI. Many children with Down Syndrome will continue to develop complications and will not be able to reach their full potential. As early as 1980, Jérôme Lejeune postulated that Down syndrome as a metabolic disease can be treated - long before chromosome 21 was sequenced (in 2000). Over 40 years later we are still debating the same question, although numerous studies have confirmed Lejeune's pioneering work.

Parents trust their doctors - it cannot be expected that all parents understand the scientific and biochemical background and connections.

In my practice I see daily

- what damage the extra chromosome creates in children with Down syndrome

- how TNI supports the health of these children in many ways

There are children who finally have enough energy to move, children who finally start to speak, children who after years of epileptic seizures are finally free of seizures, children who wake up and take part in life and thus have optimal conditions for learning.

It is time that the complexity of Down syndrome is finally recognized worldwide and that the guidelines are adapted to the studies that are available on TNI so far. This includes routine testing of all nutrients that are commonly deficient, as well as standardized testing and treatment of elevated levels of free radicals. We urgently need comprehensive studies on the current TNI protocol - the Dutch report motivated me again to finally carry out a corresponding study together with the Trisomy 21 Research Foundation. Furthermore, the publication of my own data in a peer-reviewed scientific article as well as the presentation of some case studies of my patients is at the top of my list of priorities for 2022.