Development of LCHF in Muscle GSDs. S.L. Reason RN MScN EdD
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1 Development of LCHF in Muscle GSDs S.L. Reason RN MScN EdD
2 McArdle Disease is a rare disease of muscle metabolism, which is caused by a deficiency of the enzyme myophosphorylase. It is equally represented in both sexes and is inherited in an autosomal recessive manner. Although present at birth, it is often not diagnosed until the third or fourth decade of life. The cardinal symptom of this metabolic myopathy is activity intolerance, with the following constellation of symptoms myalgia, untimely fatigue, stiffness and weakness of involved muscles, along with dyspnea and tachycardia upon exertion. The acute crisis described can result in rhabdomyolysis, myoglobinuria, and acute renal failure and compartment syndrome. Second wind is a unique feature of McArdles. At approximately 8-10 minutes after activity is initiated, the body switches to alternative metabolic pathways (liver glycogen, blood glucose, free fatty acids)
3 Current Dietary Recommendation u65% complex CHO; 20% Fat; 15% Protein* uacute intake of 37g of sucrose 5 min prior to short-term intense activity (twice weekly)** *Andersen ST and Vissing J (2008) Carbohydrate and protein-rich diets in McArdle disease: effects on exercise capacity. J Neurol Neurosurg Psychiatry [doi: /jnnp ] **Andersen ST et al. (2008) Effect of oral sucrose shortly before exercise on work capacity in McArdle disease. Arch Neurol 65:
4 Because individuals with McArdle s are unable to access muscle glycogen, (80% of stored CHO) it is impossible to meet the demand for ATP, both at the beginning of activity and when the intensity of sustained activity increases An alternative fuel is therefore required, especially prior to second wind
5 Can a LOW CARBOHYDRATE HIGH FAT DIET improve activity tolerance in McArdle disease?
6 Proof of Concept Research Online survey (2016) Demographic Info Subjective experience with ketosis Case Series (2017)
7 SURVEY (n=71) Day-to-Day Impact 79% reported improvement of everyday symptoms (ADL) 69% reported feeling as though they were in permanent second wind 76% reported improvement in exercise tolerance
8 Case Series Reason SL, Westman EC, Godfrey R, & MaGuire E. (2017) Can a Low- Carbohydrate Diet Improve Exercise Tolerance in McArdle Disease? J Rare Disorders Diagnosis & Therapy, 3:1.
9 Case Gender Current Age Age symptoms first presented Age at Diagnosis PYGM Mutations 1 M p.r50x; p.r50x 2 F p.r50x; p.leu397pro 3 F p.r50x; p.thr672iie
10 Table 2: Clinical response: Not in ketosis and while in ketosis Case Not in Ketosis In Ketosis CK Exercise Tolerance CK Exercise Tolerance U/L From childhood, would have to stop due to muscle pain, especially early in any activity or if there was an incline. Walking or cycling uphill was always a challenge, with pain starting in the legs and progressing to the upper body until there would be no alternative but to stop and rest. 236 U/L* Exercise intolerance is distinctly less. Can start walking at a faster pace in ketosis. Is able to jog and exercise on a completely different level. Limits are now more down to basic fitness level, rather than due to McArdles. There is no question a LCKD has improved both aerobic and anaerobic activity tolerance. 2 22,271 U/L Upon diagnosis, was advised to begin a high carbohydrate diet. Within a few months, exercise intolerance worsened. Began to have problems in daily activities, like walking, eating, bathing and playing. After a few months needed to use a wheelchair four days/week due to muscle damage of the leg muscles. 494 U/L Exercise tolerance dramatically improved once in ketosis. However due to prolonged inactivity while on a high carbohydrate diet, it has taken a few months to regain aerobic fitness. Personal care, playing with other kids, attendance at school have been dramatically improved on a LCKD. Use of a wheelchair is no longer required, therefore; PE classes have been restarted. 3 10,744 U/L Experienced muscle failure, muscle spasm and flu-like symptoms regularly. With age, muscle pain was more prevalent. ADLs would cause fatigue and muscle cramps. Exercise seemed to get harder and harder to maintain with age. 150 U/L* Overall CK is much lower while on a LCKD. No longer experience flu-like symptoms.. There is no need to wait until 'second wind'. Aerobic and anaerobically activities are easier, no longer suffering from muscle aches and pain afterwards. Reference Range: Males >18 years: U/L; Females 8-14 years: U/L & > 18 years: U/L *within normal reference range
11 CHO stimulate insulin secretion, which facilitates the acute use of CHO as a fuel substrate and drives fat storage Consumption of dietary CHO seems to exacerbate activity intolerance in each of the three described cases
12 Adoption of a LCHF diet up-regulates fat metabolism and seems to improve activity and exercise tolerance for patients with McArdle disease ADLs more manageable Exercise tolerance is improved Potentially minimize the risk of secondary conditions (CHD, hypertension, obesity, atheroma, stroke, cancer, etc.) associated with physical inactivity & dietary sugar
13 These findings support the need for clinical research to explore the use of LCHF in McArdle disease
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