Scurvy, vitamin C and autism

I'd been thinking about writing this post on scurvy, vitamin C and autism for quite a while. The paper by Kitcharoensakkul and colleagues [1] really made the decision for me, following their discussions on three young children with walking difficulties who were eventually diagnosed with scurvy, one of whom was diagnosed with autism. The authors concluded: "These clinical manifestations and radiologic findings highlight the importance for rheumatologists to have a higher index of suspicion for scurvy in nonambulatory children". Nonambulatory by the way, means not able to walk about (independently). "Interestingly, all patients had concomitant vitamin D deficiency" was another important point made in the Kitcharoensakkul study which is something I'm always a little interested in on this blog (see here).

Limes... @ Fludkov @ Wikipedia 

Scurvy, as some people might already know, is a condition characterised by a lack of sufficient vitamin C (ascorbic acid). It can manifest in a variety of ways including fatigue, lack of appetite, irritability alongside various functional gastrointestinal (GI) symptoms. Gingival swelling or bleeding (the gums) is perhaps one of the best known [oral] signs of the disease. Nowadays it is quite a rare condition.

In other blog entries I've referred to myself as a Limey reflective of a slang phrase for someone from these hallowed Isles called Great Britain (Britain, Britain, Britain..), which seems to derive from the practice of giving lime juice to British sailors way back when, to prevent scurvy.

Suffice to say however that the Kitcharoensakkul paper is not the first time that scurvy has appeared alongside the word autism or words autism spectrum disorder (ASD) as I'll attempt to show you...

• Case studies describing scurvy concurrent to a diagnosis of autism can be found in the peer-reviewed research literature [2]. The description by Mawson [3] is typical although some symptoms reported in that particular case as being perhaps complicated by "treatment with indomethacin, which lowers vitamin C levels" is an important addition. I do think it is important to raise the point that some medicines can interfere with the availability of things like vitamins and minerals similar to such nutraceuticals affecting some medicines.
• Cole and colleagues [4] talked about the continued presence of scurvy "among susceptible populations" which includes "certain unique populations-particularly the elderly subjects, patients with neurodevelopmental disabilities or psychiatric illnesses, or others with unusual dietary habits" in their report on a "10-year-old autistic child". 'Unusual' dietary patterns are no stranger to autism [5] (open-access here) over and above any special dietary regimes being implemented (see here).
• Congidi and colleagues [6] described another case of scurvy in "an autistic child with food-avoidant behavior". They also described MRI findings for their patient. Indeed, this is something also described in the report by Tetsu and colleagues [7] who reported that the: "imaging findings of the thigh showed diffuse signal abnormality in the bone marrow, periosteum, and the femoral muscle". Further: "A biopsy specimen of the femur showed hematoma, proliferative fibroblasts, and few collagen fibers, which suggested a deficiency of vitamin C".
• Slightly outside of the issue of scurvy is the study presented by Dolske and colleagues [8] "exploring the effectiveness of ascorbic acid (8g/70kg/day) as a supplemental pharmacological treatment for autistic children in residential treatment". Although this was a small trial in terms of participant numbers, it was a "double-blind, placebo-controlled trial" lasting 30 weeks. The authors reported "a reduction in symptom severity associated with the ascorbic acid treatment" making specific mention of "sensory motor scores". Obviously I'm not making any recommendations about these findings (no medical or clinical advice given or intended) but do find them to be interesting and perhaps overlapping with other research where vitamin C supplementation has been included. So, think back to the Jim Adams trial data (see here) based on some older research [9]. As to the hows and whys, well, unlike the chatter about vitamin C therapy potentially impacting on Epstein-Barr antibodies no biological measure was used in the Dolske study so we are left speculating...

As you've probably realised, most of the research evidence surrounding the presence of scurvy in cases of autism is based on individual case reports. I can't for example, provide you with any population estimates of how prevalent scurvy might be in cases of autism because no-one has really looked at this issue with any great assiduity. I can point you in the direction of other work talking again about cases of scurvy appearing alongside schizophrenia for example [10] but will only say that a poor diet lacking in sources of vitamin C is as much to blame in those examples as it probably is where cases of autism are discussed.

Just before I go, there are a few other things to note about vitamin C and autism which may also be pertinent to other issues. I've talked about iron before on this blog and how there is some data suggesting issues with iron for some on the autism spectrum (although certainly not all). It's quite long been recognised that vitamin C also plays a role in the absorption of iron [11] particularly non-heme iron sources and a deficiency in vitamin C is probably not going to be conducive to 'optimal' function. Quite a while back I also talked about autism and oxalates (see here) but will say no more than re-iterating the study by Chai and colleagues [12] with the requirement for lots more investigation in this area.

To close, I was saddened to hear of the death of Prof. Paul Patterson this week, a real research pioneer who's studies on autism and schizophrenia were frequently discussed on this blog (see here and see here). One of his final research contributions was the very important study fronted by Elaine Hsiao supporting a "gut-microbiome-brain connection in a mouse model of ASD". My condolences go to his family and those who knew him.

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[1] Kitcharoensakkul M. et al. Scurvy revealed by difficulty walking: three cases in young children. J Clin Rheumatol. 2014 Jun;20(4):224-8.

[2] Monks G. et al. A case of scurvy in an autistic boy. J Drugs Dermatol. 2002 Jul;1(1):67-9.

[3] Mawson AR. Bone pain, growth failure, and skin rash after an upper respiratory illness in a boy with autism: possible association with altered retinoid metabolism. Clin Pediatr (Phila). 2009 Jan;48(1):21-5.

[4] Cole JA. et al. Scurvy in a 10-year-old boy. Pediatr Dermatol. 2011 Jul-Aug;28(4):444-6

[5] Bandini LG. et al. Food selectivity in children with autism spectrum disorders and typically developing children. J Pediatr. 2010 Aug;157(2):259-64.

[6] Gongidi P. et al. Scurvy in an autistic child: MRI findings. Pediatr Radiol. 2013 Oct;43(10):1396-9.

[7] Tetsu N. et al. curvy in a Child With Autism: Magnetic Resonance Imaging and Pathological Findings. Journal of Pediatric Hematology/Oncology. 2012; 34: 484-487.

[8] Dolske MC. et al. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993 Sep;17(5):765-74.

[9] Adams JB. & Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med. 2004 Dec;10(6):1033-9.

[10] Dubé M. Scurvy in a man with schizophrenia. CMAJ. Aug 9, 2011; 183(11): E760.

[11] Hallberg L. et al. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-8.

[12] Chai W. et al. Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium oxalate stone formers and non-stone formers. AJKD. 2004; 44: 1060-1069.

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Kitcharoensakkul M, Schulz CG, Kassel R, Khanna G, Liang S, Ngwube A, Baszis KW, Hunstad DA, & White AJ (2014). Scurvy revealed by difficulty walking: three cases in young children. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 20 (4), 224-8 PMID: 24847751