Nutritional Epigenetics

This little video beautifully explains the concept of nutritional epigenetics. Working with international researchers, we published in 2013 a review on this topic:

Jalili M, Pati S, Rath B, Bjørklund G, Singh RB. Effect of Diet and Nutrients on Molecular Mechanism of Gene Expression Mediated by Nuclear Receptor and Epigenetic Modulation. Open Nutra J 2013;6:27-34.

Zinc, Copper, and Autism Spectrum Disorder

Joint Research

Research indicates that children with autism spectrum disorder (ASD) appear to be at risk for zinc (Zn) deficiency, copper (Cu) toxicity, and often disturbed metallothionein system functioning (1-4). Working with international researchers, the following is a summary of our work.

Li et al. (2014) investigated the serum levels of Zn and Cu in 60 Chinese children with ASD (48 boys, 12 girls) and a control group of 60 healthy sex-matched and age-matched individuals (2). The researchers also evaluated the autism severity using the Childhood Autism Rating Scale (CARS) score. The mean serum Zn levels and Zn/Cu ratio in the study were significantly lower in the ASD children compared with the control group (P<0.001). At the same, the serum Cu levels were significantly higher in the ASD children compared with the control group (P<0.001). It was in the study found a significant negative association between the Zn/Cu ratio and CARS scores (r=-0.345, P=0.007) (2).

Macedoni-Lukšič et al. (2015) determined the serum levels of Zn and Cu in a group of Slovenian children with ASD (N = 52, average age = 6.2 years) and a control group of children with other neurological disorders (N = 22, average age = 6.6 years), matched in terms of intellectual abilities (3). Compared to the control group, the ASD group had significantly elevated serum Cu/Zn ratio (95% confidence interval for children with ASD=1.86-2.26; 95% confidence interval for the control group=1.51-1.88) (3).

Crăciun et al. (2016) investigated the levels of Zn and Cu in whole blood, as well as the Cu/Zn ratio in a group of 28 Romanian ASD children. No significant difference in whole blood Cu was observed. However, Cu/Zn ratio was ~15 % (p = 0.008) higher in ASD children than that in the control ones. The results of the study may be indicative of Zn deficiency in ASD children (4).

In conclusion, our research suggests that providing Zn to ASD children may be an important component of a treatment protocol, especially in children with Zn deficiency (1-4). Mercury accumulation may occur as a cause or consequence of metallothionein dysfunction in ASD children, which may be one of the causes of Zn deficiency. Metallothioneins are proteins with important functions in metal metabolism and protection. It is important to monitor and follow the values for both Cu and Zn together during Zn therapy because these two trace elements are both antagonists in function, and essential for living cells (1).

– Geir Bjørklund

 

References

1. Bjørklund G. The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp 2013; 73: 225–236.

2. Li SO, Wang JL, Bjørklund G, Zhao WN, Yin CH. Serum copper and zinc levels in individuals with autism spectrum disorders. Neuroreport 2014; 25: 1216-1220.

3. Macedoni-Lukšič M, Gosar D, Bjørklund G, Oražem J, Kodrič J, Lešnik-Musek P, Zupančič M, France-Štiglic A, Sešek-Briški A, Neubauer D, Osredkar J. Levels of metals in the blood and specific porphyrins in the urine in children with autism spectrum disorders. Biol Trace Elem Res 2015; 163: 2-10.

4. Crăciun EC, Bjørklund G, Tinkov AA, Urbina MA, Skalny AV, Rad F, Dronca E. Evaluation of whole blood zinc and copper levels in children with autism spectrum disorder. Metab Brain Dis 2016; 31: 887-890.

Healing of Amyotrophic Lateral Sclerosis: A Case Report

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive and fatal neurodegenerative disease that causes selective motor neuron death. Mercury toxicity has been suggested as a possible risk factor for ALS and other neurodegenerative disorders.

Three of the members of the CONEM Germany Environmental Health and Safety Research Group published this case report recently in the peer-reviewed journal Complementary Medicine Research.

 

Inge Mangelsdorf, Harald Walach, and Joachim Mutter

Healing of Amyotrophic Lateral Sclerosis: A Case Report

Complement Med Res 2017; 24(3): 175-181

 

ABSTRACT

Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to death within 3–5 years in most cases. New approaches to treating this disease are needed. Here, we report a successful therapy.

Case Report: In a 49-year-old male patient suffering from muscle weakness and fasciculations, progressive muscular atrophy, a variant of ALS, was diagnosed after extensive examinations ruling out other diseases. Due to supposed mercury exposure from residual amalgam, the patient’s teeth were restored. Then, the patient received sodium 2,3-dimercaptopropanesulfate (DMPS; overall 86 × 250 mg in 3 years) in combination with α-lipoic acid and followed by selenium. In addition, he took vitamins and micronutrients and kept a vegetarian diet. The excretion of metals was monitored in the urine. The success of the therapy was followed by scoring muscle weakness and fasciculations and finally by electromyography (EMG) of the affected muscles. First improvements occurred after the dental restorations. Two months after starting therapy with DMPS, the mercury level in the urine was increased (248.4 µg/g creatinine). After 1.5 years, EMG confirmed the absence of typical signs of ALS. In the course of 3 years, the patient recovered completely.

Conclusions: The therapy described here is a promising approach to treating some kinds of motor neuron disease and merits further evaluation in rigorous trials.

 

Only One-Fifth of Global Population Achieves Sufficient Vitamin E Status to Receive Functional Health Benefits

A recent study published in the International Journal for Vitamin and Nutrition Research (1) establish that just 21% of the studies of the examined populations globally reach a serum α-tocopherol concentration of ≥30 μmol/L. This is the vitamin E threshold that several studies suggest has major effects on human health in multiple areas. The research is unique, and the first of its kind to review over 170 existing papers worldwide on studies into vitamin E intake levels and serum concentrations. The findings conclude that vitamin E status is inadequate in a substantial part of the reviewed populations. Infographic: Vitamin E status remains low in most countries

Vitamin E StatusVitamin E is an essential micronutrient that protects cell membranes from oxidative damage, including those rich in polyunsaturated fatty acids (PUFAs). The higher the level of PUFA intake, the more vitamin E is required. This study finds vitamin E status to be alarmingly low globally. Modern changes in diet may be a contributing factor. Vitamin E status can be increased by eating more foods high in vitamin E, such as vegetable oils, green vegetables, nuts, seeds, whole grain bread; fortified foods and beverages, and dietary supplements.

Dr. Simin Meydani, Director of Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University comments: “This global assessment of vitamin E status – the first of its kind – is an important step to generate awareness because so many people around the world do not consume recommended amounts of vitamin E. An adequate vitamin E intake is needed to maintain the immune system, cognitive function, cardiovascular health, and liver function. The findings of the publication suggest that health authorities need to dedicate more attention to the intake, status, and role of vitamin E in human health.”

Applying a Recommended Daily Allowance (RDA) of 15 mg/day and Estimated Average Requirement (EAR) of 12 mg/day to all populations with a minimum age of 14 years, 82% and 61% of data points were below the RDA and EAR respectively. The new paper further reveals that globally 13% of the scientific publications indicated serum concentrations below the suggested deficiency threshold concentration of 12 μmol/L, mostly in newborns and children.

Szabolcs Péter, MD, PhD, Senior Scientist at DSM, and one of the co-authors says: “This comprehensive review of vitamin E dietary intake and serum concentrations demonstrates that the majority of the reported intake values worldwide are below recommended levels. Similarly, it shows that a considerable proportion of the global population do not reach the proposed optimal serum concentration for vitamin E. This study should help stimulate needed research to understand the complex field of vitamin E and its impact on human health.”

The study found that vitamin E intake differed regionally. People living in the Middle East and Africa (27%) were more likely to be consuming below the RDA, but the prevalence was also relatively high in Asia Pacific (16%) and Europe (8%). Considering a threshold concentration of 30 μmol/L recommended by experts, 27% of the American, 80% of the Middle East/African, 62% of the Asian, and 19% of the European populations are below this serum value. On the other hand, only 21% of the total data points included in this global review reach a desirable mean serum concentration of 30 μmol/L or higher. This can be explained by varying diets and nutrient availability across the world.

Reference

1. Szabolcs P, Angelika F, Roos FF, Wyss A, Eggersdorfer M, Hoffmann K, Weber P. A Systematic review of global alpha-tocopherol status as assessed by nutritional intake levels and blood serum concentrations. Int J Vitam Nutr Res 2016. DOI: 10.1024/0300-9831/a000281.

Digestive Enzyme Therapy: A Possible Option in Autism Spectrum Disorder

There is growing evidence for a gut-brain connection associated with autism spectrum disorder (ASD), which suggests a potential benefit for digestive enzyme therapy in autistic children (1). Working with an Egyptian team, Geir Bjørklund and collaborators performed a double-blind, randomized clinical trial on 101 children with ASD (82 boys and 19 girls) aged from 3 to 9 years (1). The autistic children were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) diagnostic criteria. Structured interviews of at least one hour were first performed both with the parents and the children. In a later two hours session was the Childhood Autism Rating Scale (CARS) applied. After this, the children with ASD were randomized to receive digestive enzymes or placebo (1). It was found that autistic children that received digestive enzyme therapy for three months had significant improvement in emotional response, general impression autistic score, general behavior, and gastrointestinal symptoms. These results indicate that digestive enzyme therapy in the future may be a possible option in the treatment protocols for ASD (1).

The first author of the article, Khaled Saad, is Associate Professor of Pediatrics at Assiut University, Assiut, Egypt. Geir Bjørklund is the founder and president of the Council for Nutritional and Environmental Medicine (CONEM).

 

Reference

1. Saad K, Eltayeb AA, Mohamad IL, Al-Atram AA, Elserogy Y, Bjørklund G, El-Houfey AA, Nicholson B. A randomized, placebo-controlled trial of digestive enzymes in children with autism spectrum disorders. Clin Psychopharmacol Neurosci 2015; 13(2): 188-193.

 

Vitamin D Deficiency Correlates with Severity of Autism and Shows Improvement with Supplementation

Vitamin D deficiency has been previously reported in patients with autism spectrum disorder (ASD). However, the data on the relationship between vitamin D deficiency and the severity of ASD are limited. In collaboration with Egyptian researchers, Geir Bjørklund (2015) performed a case-controlled cross-sectional analysis on 122 children with ASD, to assess their vitamin D status compared to healthy control children and the relationship between the degree of vitamin D deficiency and the severity of ASD (1).

Fifty-seven percent of the patients with ASD in the study had vitamin D deficiency, and 30% had vitamin D insufficiency. The vitamin D levels in the children with severe ASD were significantly lower than those in children with mild/moderate ASD. It was found that the vitamin D levels had significant negative correlations with the Childhood Autism Rating Scale (CARS) scores (1).

106 children with low serum vitamin D levels (<30 ng/ml) then participated in an open-label trial of vitamin D supplementation. The patients were given 300 IU/kg/day (not to exceed 5000 IU/day) for three months. Eighty-three ASD patients completed three months of daily vitamin D treatment. 80.72% (67/83) of the children with ASD who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the Childhood Autism Rating Scale and aberrant behavior checklist subscales that measure behavior, stereotype, eye contact, and attention span (1). Of the 16 parameters measured, ten showed highly statistically significant improvements (see table below).

 

Parameter  P Value (* highly statistically significant)
Relating to people <0.001*
Emotional Response <0.001*
Imitation <0.001*
Body use 0.01*
Object use 0.01*
Adaption to change 0.004*
Listening response 0.01*
Taste, smell, touch 0.1
Visual response 0.003*
Fear 0.13
Verbal communication 0.3
Activity level 0.32
Non-verbal communication 0.2
Intellectual response 0.1
General impression <0.001*
Total CARS score <.001*

 

The researchers concluded that as vitamin D is inexpensive, readily available and safe it may have beneficial effects in ASD patients, particularly when the final serum level is more than 40 ng/ml (1). It should be noted that these results were achieved after only three months of vitamin D supplementation. In a condition that is often present at birth and lasts a lifetime, this is a highly significant finding and should be fully explored immediately.

The first author of the study, Khaled Saad, is Associate Professor of Pediatrics at Assiut University, Assiut, Egypt. Geir Bjørklund is founder and president of the Council for Nutritional and Environmental Medicine (CONEM). Also, one of the coauthors is John Cannell, MD. He is the founder of the Vitamin D Council in San Luis Obispo, California, United States. The study is registered in UMIN Clinical Trials Registry: UMIN000016770.

 

Reference

1. Saad K, Abdel-rahman AA, Elserogy YM, Al-Atram AA, Cannell JJ, Bjørklund G et al. Vitamin D Status in Autism Spectrum Disorders and the Efficacy of Vitamin D Supplementation in Autistic Children. Nutr Neurosci. Article first published online: 15 Apr 2015. DOI: http://dx.doi.org/10.1179/1476830515Y.0000000019.

 

Serum Zinc and Copper Levels in Autistic Children

NeuroReport 25 (15) 2014In collaboration with Chinese researchers, Geir Bjørklund investigated the serum levels of zinc (Zn) and copper (Cu) in 60 Chinese children with autism (48 boys, 12 girls) and a control group of 60 healthy sex-matched and age-matched individuals. The researchers also evaluated the severity of autism using the Childhood Autism Rating Scale (CARS) score. The mean serum Zn levels and Zn/Cu ratio in the study were significantly lower in the autistic children compared with the control group (P<0.001). At the same time were the serum Cu levels significantly higher in the autistic children compared with the control group (P<0.001). It was in the study found a significant negative association between the Zn/Cu ratio and CARS scores (r=-0.345, P=0.007). 

The original article is published in NeuroReport (2014; 25 (15): 1216–1220). Bjørklund is founder and president of Council for Nutritional and Environmental Medicine (CONEM).

 

Si-Ou Li, Jia-Liang Wang, Geir Bjørklund, Wei-Na Zhao, and Chang-Hao Yin

Serum copper and zinc levels in individuals with autism spectrum disorders

Neuroreport 2014; 25 (15): 1216-1220

 

ABSTRACT

Trace elements play a critical role in the pathogenesis of autism spectrum disorders (ASD). The aim of this study was to investigate the serum levels of zinc (Zn) and copper (Cu) in Chinese children with ASD. Sixty patients (48 males, 12 females) diagnosed with ASD and 60 healthy sex-matched and age-matched control participants were assessed for serum Zn and Cu content at admission. The severity of ASD was also evaluated using the Childhood Autism Rating Scale (CARS) score. The results indicated that the mean serum Zn levels and Zn/Cu ratio were significantly lower in children with ASD compared with normal cases (P<0.001, respectively), whereas serum Cu levels were significantly higher (P<0.001). There was a significant negative association between Zn/Cu and CARS scores (r=-0.345, P=0.007). On the basis of the receiver operating characteristic curve, the optimal cut-off value of serum levels of Zn/Cu as an indicator for an auxiliary diagnosis of autism was projected to be 0.665, which yielded a sensitivity of 90.0% and a specificity of 91.7%; the area under the curve was 0.968 (95% confidence interval, 0.943-0.993). In conclusion, these results suggested an association between serum levels of Zn and Cu and ASD among Chinese patients, and the Zn/Cu ratio could be considered a biomarker of ASD.

 

The Role of Zinc and Copper in Autism Spectrum Disorders

Acta Neurobiol Exp 2013, 2Children with Autism spectrum disorders (ASDs) appear to be at risk for zinc (Zn) deficiency, copper (Cu) toxicity, have often low Zn/Cu ratio, and often disturbed metallothionein (MT) system functioning. The evidence presented in this paper suggests that providing Zn to autistic children may be an important component of a treatment protocol, especially in children with Zn deficiency. It is important to monitor and follow the values for both Cu and Zn together during Zn therapy, because these two trace elements are both antagonists in function, and essential for living cells. 

The review article by Geir Bjørklund is published in Acta Neurobiologiae Experimentalis (2013; 73 (2): 225–236). This peer-reviewed journal is published by Nencki Institute of Experimental Biology in Warsaw, Poland. Bjørklund is founder and president of Council for Nutritional and Environmental Medicine (CONEM).

 

Geir Bjørklund

The role of zinc and copper in autism spectrum disorders

Acta Neurobiol Exp (Wars) 2013; 73 (2): 225-236 

 

ABSTRACT

Autism spectrum disorders (ASDs) are a group of developmental disabilities that can cause significant social, communication and behavioral challenges. Several studies have suggested a disturbance in the copper (Cu) and zinc (Zn) metabolism in ASDs. Zinc deficiency, excess Cu levels, and low Zn/Cu ratio are common in children diagnosed with an ASD. The literature also suggests that mercury accumulation may occur as a cause or consequence of metallothionein (MT) dysfunction in children diagnosed with an ASD, which may be one of the causes of Zn deficiency. MTs are proteins with important functions in metal metabolism and protection. Zinc and Cu bind to and participate in the control of the synthesis of MT proteins. Studies indicate that the GABAergic system may be involved in ASDs, and that Zn and Cu may play a role in this system.