Nations SP, Boyer PJ, Love AMF, Butz JA, Wolfe GI, Hynan LS, Reisch J, Tivedi JR. An unusual source of excess zinc, leading to hypocupremia and neurologic disease. Neurology. 2009; 73:(1)
Greenberg SA, Briemberg HR. A neurological and haematological syndrome associated with zinc excess and copper deficiency. J Neurology. 2008; 71:(1)
The body requires zinc in small amounts to remain healthy. Because the body balances zinc and copper, people who ingest excessive zinc have resulting dangerously low levels of copper. An acute zinc overdose itself may be toxic and chronic zinc ingestion results in bone marrow suppression and degeneration of the spinal cord, usually resulting in crippling nerve damage. It's been called ‘human swayback disease’. A case of a 54-year-old female whose nerve damage greatly reduced her mobility due to copper deficiency myelopathy as a result of the use of denture fixative cream is discussed.
Clinical Relevance: Many cases of mysterious nerve damage turn out to be caused by overuse of popular denture products, eg Fixodent. Thus we are encouraging patients to read the manufacturer's leaflet and follow the instructions carefully.
Article
Zinc is a mineral which the body requires in small amounts from the diet to remain healthy. It is essential for sustaining life. The body uses zinc-containing enzymes to regulate growth, promote fertility and to aid in digestion.
Zinc is also needed for nucleic acid synthesis. The body requires zinc in the tissues where new cell development takes place, such as the bone marrow, immune cells and the lining of the gut.
When zinc is consumed in large amounts it causes zinc poisoning and can also result in the depletion of copper and iron. An acute zinc overdose itself may be toxic and chronic zinc ingestion results in bone marrow suppression and degeneration of the spinal cord, usually resulting in crippling nerve damage. It's been called ‘human swayback disease.’1,2 It may also cause a widespread neuropathy. Excessive use of denture adhesive cream can result in the consumption, and so absorption of, excess zinc.1
Case report
This case report describes the progressive neurological deterioration of a patient over a 4-year period resulting in weakness in the legs, widening gait and general unsteadiness. The patient was diagnosed and treated for various neurological conditions before the link of her worsening neurological condition with excess use of Polygrip Ultra was made.
History
In May 2009, a 54-year-old female, Caucasian patient (Patient X) was referred to the maxillofacial department in Falkirk and District Royal Infirmary by her general dental practitioner (GDP) regarding an area of denture hyperplasia in the mandibular anterior region, which was affecting the stability of her lower denture (Figure 1).
Figure 1. Area of mandibular denture-induced hyperplasia.
Patient X presented complaining of ill-fitting complete upper and lower dentures. Her current dentures were over 10 years old and were so ill-fitting that she used a denture fixative cream every day to hold them in place. Her GDP had referred her to the department as he wanted the area of hyperplasia removed before constructing new dentures.
Patient X was a 54-year-old female who was an ex-smoker. She had a complex medical history. She reported that she had mild asthma and used inhalers on demand. She also said that she had been taking a copper supplement for her neurological disability for the past year. Her worsening neurological state and on-going weakness meant that she now needed a delta frame to walk and could only manage a few steps unaided. She reported that she had started to develop her neurological symptoms in October 2005.
She had been investigated by the local neurology department since March 2006 for weakness in her legs. She was also experiencing unsteadiness and a widened gait. The neurology diagnosis was one of new onset ataxia with pyramidal tract and post column sign.
The investigations requested by the neurology department showed minor hyper-intensities in the cerebral hemisphere and the pons. The spinal cord appeared normal.
A diagnosis of a suspected autoimmune disease, such as a vasculitis of the spinal cord, was made. However, the blood result for the auto-antibodies was negative. A low thyroid-stimulating hormone (TSH) and low serum copper (7 µmol/l) were also detected.
The patient was then referred to a consultant physician as a result of the low TSH and serum copper. At this consultation a link was made between the neurological symptoms and hyperthyroidism, and Graves' disease. This resulted in patient X being prescribed carbimazole.
By June 2008, her neurological condition was continuing to deteriorate. Continued testing showed persistent low serum copper. The diagnosis of a copper deficiency myelopathy was made and patient X was put on a copper supplement.
A copper deficiency is increasingly recognized as a rare cause of a clinical picture similar to sub-acute combined degeneration of the spinal cord. The neurology consultant discussed the case with the clinical biochemists with regard to the ongoing mal-absorption of copper.
The biochemist had also noticed an increased serum zinc level. It is known that excessive zinc interferes with the absorption of copper.
The question was then raised as to how this patient had an increased zinc level. During one consultation her sister made an interesting observation that she was wearing an ill-fitting lower denture and used a denture fixative cream, Poligrip Ultra, daily.
The ingredients of Poligrip Ultra were listed as Poly (Methylvinylether/Maleic acid) and Na-Mg-Zn mixed partial salt.
At the same time the biochemist found a paper entitled: ‘Denture cream: an unusual source of excess zinc, leading to hypocupremia and neurologic disease’.3 The biochemistry department had also recently picked up another patient with a copper deficiency myelopathy which was attributed to excessive use of denture fixative cream.
The link was then made between excess use of denture fixative cream, hypocupremia and myelopathy. Patient X was advised to stop using the cream. Within 3 months her serum copper levels started to improve, as did the serum zinc. Patient X was able to reduce the copper supplement. She was also advised to stop carbimazole after an 18-month course. Her mobility and neurological symptoms also began to resolve.
In October 2009, Patient X had the area of denture hyperplasia excised from the mandibular ridge carried out under local anaesthesia in the maxillofacial department. On review, her mouth had healed well and the pathology confirmed the diagnosis of denture hyperplasia.
Discussion
For healthy adults, the daily recommended amount of zinc ranges from 12–15 mg. Most people achieve this through eating a healthy, balanced diet. Patients with deficiencies are advised to take dietary supplements to increase their zinc intake and zinc is included in most multi-vitamin tablets.
When hyperzincaemia is diagnosed, it is often difficult to determine the cause. Although it is a heavy metal, it is difficult to overdose through dietary means alone, or indeed through supplements, as approximately 8–10 times the daily amount is required before zinc poisoning occurs.
Zinc is an intestinal irritant and the first sign of acute zinc poisoning is usually nausea and vomiting. Chronic, excess ingestion can cause neurological damage, such as numbness, tingling or weakness in the arms and legs, difficulties with walking and balance and blood problems, such as anaemia.
Excess zinc is also a recognized cause of copper deficiency resulting from competitive inhibition of gastro-intestinal absorption. A patient with zinc excess and copper deficiency would show characteristic haematological syndrome of copper deficiency and a neurological syndrome of a myelopathy, and generalized lower motor neuron involvement, as was seen with Patient X.4
In this case, Patient X was wearing ill-fitting upper and lower complete dentures for about 10 years and, to hold her denture in place, she was using Poligrip Ultra denture fixative cream. Poligrip Ultra comes in 68 g tubes. She typically applied Poligrip Ultra three times per day and consumed between one-and-a-half and two tubes per week.
The recommended instruction for use of Polygrip Ultra cream by GlaxoSmithKline is a once daily application of a typical amount of 0.5–1.5 g of the cream to the fitting side of the denture. Therefore, a 68 g tube would be expected to last for 3–5 weeks.
Poligrip Ultra cream contains at least 17 mg of zinc per gram of cream. Application of one and a half to two standard 68 g tubes per week would lead to exposure to at least 1734–2312 mg of zinc per day.
Polygrip Ultra strips are an easier and more accurate way of using the product (Figure 2).
Figure 2. Patient X's dentures with Polygrip Ultra cream on fitting surface. Also shown are Polygrip Ultra strips.
Conclusions
Patients should be encouraged to register with a GDP even if they are edentulous and should be reviewed at least on a bi-annual basis.5
Registration with a dentist would have identified this patient's difficulties with her ill-fitting dentures and possibly her excessive use of denture fixative creams. Certainly, a newly constructed set of dentures would have negated the need for a fixative cream.
Patients with ill-fitting dentures should have them replaced rather than depending on a fixative cream but, in the case of when they might use such a product, educating patients to read leaflets carefully and to follow the manufacturer's instructions is of paramount importance. There are also different varieties of product on the market, with the individually wrapped strips offering a more accurate method of applying the product.
In this case report, excess use of PoliGrip Ultra denture fixative cream by Patient X caused hyperzincaemia with associated hypocupremia, resulting in serious neurological damage. While the haematological irregularities were corrected with cessation of use of the product, the neurologic symptoms took longer to abate.
The risk of zinc poisoning from the Polygrip Ultra (and similar products) prompted GlaxoSmithKline to announce it would voluntarily stop manufacturing, marketing and advertising three zinc-containing Super PoliGrip denture cream products on 18 February 2010. The products were Super PoliGrip ‘Original’, ‘Ultra Fresh’ and ‘Extra Care’. The company said it would investigate reformulating Super PoliGrip ‘Original’, Super PoliGrip ‘Ultra Fresh’ and Super PoliGrip ‘Extra Care’ to non-zinc formulations. The new versions were available from 2010. Glaxo maintains that Super PoliGrip ‘Original’, ‘Ultra Fresh’ and ‘Extra Care’ are safe to use as directed, but noted that some consumers may apply more adhesive than directed, or use it more than once per day. In a statement posted on its website, Glaxo said it stopped the manufacture, distribution and advertising of the three zinc-containing Super PoliGrip products as a precautionary measure to minimize any potential risks to consumers. The company also said it had discussed the matter with the Food and Drug Administration (FDA), and no further action is necessary.
