vitamin D supplementation preventing falls

Vitamin D has direct effects on muscle strength modulated by specific vitamin D receptors in muscle tissue. Clinical trials of older individuals at risk of vitamin D deficiency show benefits form taking vitamin D supplements on strength, funciotn and balance in a dose related pattern,
HA Bischoff-Ferrari et al have reviewed publications in this topic to test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals.
Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D3 (cholecalciferol) orvitamin D2 (ergocalciferol)) or an active form of vitamin D (la-hydroxyvitamin D3 (la-hydroxycalciferol) or 1,25-dihydroxyvitamin D3 (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion.
Eight randomised controlled trials (n=2426) of supplemental vitamin D met their inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D3 concentration (25(OH)D concentration: <60 nmol/I v ~60 nmol/I; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% Cl 0.71 to 0 . .92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/I or more resulted in a 23% fall reduction (0.77, 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (1.10, 0.89 to 1.35; n=505 from
WHAT IS ALREADY KNOWN ON THIS TOPIC
Recent systematic reviews suggest a non-significant reduction in falls among individuals receiving supplemental vitamin D
Vitamin D has a direct beneficial effect on muscle, and improved strength and balance in several trials in older persons
WHAT THIS STUDY ADDS
A dose of700-1000 IU supplemental vitamin D a day reduced falls by 19%, and by up to 26% with vitamin D3' within 2-5 months of treatment initiation
Vitamin D may not reduce falls at doses of less than 700 IU a day. Active forms of vitamin D do not appear to be more effective for fall prevention than 700-1000 IU of supplemental vitamin D
HA Bischoff-Ferrari et 2009 Fall prevention with supplemental and active forms of vitamin D: a meta analysis of randomised controlled trials. BMJ vol 339 pp 843-846

key events dose-response analysis in nutrition

I have always felt that by reading papers from other scientific disciplines it is possible to learn new techniques which are well tried in another context . A series of 3 papers in Critical reviews in Food Science and Nutrition is a case in point.
The papers are applied to thresh hold intakes for toxins, but one paper discusses the metabolism and dosage of Vitamin A, inadequate and toxic intakes.
These papers are to my mind very important and have wide applicability in Nutrition research


THE KEY EVENTS DOSE-RESPONSE FRAMEWORK
Due to limitations that all studies have, it is not possible to prove the existence of a biological threshold by observation alone Therefore an alternative approach is required.
The approach adopted is based on the concept of the mode of action (MOA), that is developing a an analytic framework based on systematic evaluation of key events. A mode of action for a biological effect is a plausible sequence of key events, starting with the interaction of an agent with a cell, through functional and anatomical changes, leading to an observed effect supported by experimental observations and mechanistic data.
A key event is defined as an observable, precursor step that is a necessary component of the mode of action, or is a marker for such change.
The relevance of a key event in a particular mode of action, and of the mode of action overall, are evaluated using a weight of evidence approach.
The individual events may include homeostatic physiological mechanism, immune response and host characteristics age, health, genetic make up, exposure patterns . What events are control pints ie rate limiting steps.
The hypothesis is that by identifying the key events for a specific toxicological effect, these would be more amenable to the experimental demonstration of a threshold than the effect itself. It would be possible to use such information on specific interventions, biological and chemical analogy, and the genetic differences in exploring the evidence for thresholds in a key event. Key events are, in principle, quantifiable by definition. An analysis of dose-response concordance should enable the identification of a rate limiting key event for the mode of action (MOA ) and whether anyone key event is the critical determinant of the response.
The importance of this approach is reflected in the views of a number of regulatory agencies.
"When adequate data on mode of action provide sufficient evidence to support a non linear mode of action for the general population and/or any subpopulations of concern ... -a reference dose/reference concentration that assumes that nonlinearityis used."
"A sufficient basis to support this nonlinear procedure is likely to include data on responses that are key events integral to the biological process."

Julien et al 2009 The key events dose-response framework : a cross disciplinary mode-of action based approach to examining dose-response and thresholds. Critical reviews in Food Science and Nutrition vol 49 issue 8 pp 682-689

Boobis et al 2009 Application of key events analysis to chemical carcinogens and non carcinogens . Critical reviews in Food Science and Nutrition vol 49 issue 8 pp 690-707

Ross et al 2009 Application of a key events dose-response analysis to nutrients : a case study with vitamin A . Critical reviews in Food Science and Nutrition vol 49 issue 8 pp 708-717

reductionism and Nutrition

In his 1972 paper "More is different", Philip Anderson claimed that the behaviour of multi-component physical systems may cannot be understood from the laws that govern their component or microscopic parts - known as emergent or complex behaviour. This idea of Andersons is different form that of Stephen Hawking, who believes that when all fundamental laws of the Universe a are understood, we will in principle be able to explain all macroscopic phenomena. Writing in Physica D, Gu and colleagues describe a physical system that o cannot be easily 'reduced and of the developing symbiosis between theoretical physics and computer science", a:
In discussing 'the understandable', Stephen Wolfram" looked at the relation between a: computation and the unfolding of the physical world. He defined as reducible those systems for which there is a logic or computational shortcut that allows their behaviour to be efficiently predicted rather than reproduced step by step. For example, the motion of a simple pendulum is described by a cosine function that can be computed using a rapidly converging mathematical series, rather than simulating each and every pendulum oscillation. But such short cuts do not usually exist for chaotic systems, g. for example.
Wolfram also pointed out that many systems are irreducible, but among them only a few are undecidable: that is they have properties that cannot be formally calculated. Undecidability is a property of universal computers or Turing machines, Macs, PCs and DNA computers all of which have unlimited memory . And this is where the notion of 'different' (or complex) systems can be made more precise - those with undecidable global properties despite having well-understood local (microscopic) governing laws.
That is that the global properties are different to the component properties.
The same thoughts could well be applied to many current problems in Nutrition
Binder 2009-10-08 The edge of reductionism Nature vol 459 pp 332-334

Alzheimer's causation

A new theory for the causation of Alzheimer’s is being promoted. An article in Nature and expanded in a review in the same journal suggests that the underlying cause of the condition is not a β-amyloid but a close relative. That an amyloid related mechanism in the brain is responsible. This prunes neuronal connections in the early part of life and may then be reactivated in old age to cause neuronal withering.
Certainly insoluble clumps of β-amyloid peptide develop in the brains of individuals with Alzheimers but also amyloid precursor proteins. This binds onto neuronal receptors setting in train the degenerative process.
Schnabel 2009 Alzheimer’s theory makes a splash Nature vol 459 p 310

Exercise and blood lipids

The influence of different types of exercise on risk factors for cardiovascular diseases has rarely been investigated. The aim of a study by Pitsavos et al in the QJM 2009 was to evaluate the effect of adding resistance exercise to aerobic activities on lipid-lipoprotein profile, in a representative sample of men and women from the province of Attica, Greece.
They randomly enrolled 1514 and 1528 healthy men and women, respectively, stratified by city, age and gender distribution. Participants were classified as inactive, sufficiently active and highly active for either aerobic activities alone or a combination of aerobic plus resistance exercise (HAC). The activities usually associated with cardiorespiratory fitness are anaerobic and activities with concentric and eccentric muscle are resistance.
The main outcome measures are lipid-lipoprotein profile [total, high-density lipoprotein (HOL) cholesterol, low-density lipoprotein (LOL) cholesterol, triglycerides, apolipoprotein-A 1, apolipoprotein-B] and anthropometric indices.
From those participating in aerobic activities, 480 (31 .7%) men and 502 (32.9%) women were classified as sufficiently active, 100 men (6.6%) and 93 women (6.1%) as highly active for either aerobic activities and 90 men (5.9%) and 49 women (3.2%) as combination of aerobic plus resistance exercise. After various adjustments were made, men from the combination of aerobic plus resistance exercise group had an average of 23% lower plasma triacylglycerol concentration (p= 0.04) and 10% lower LDL-cholesterol (P= 0.01) when compared with the highly active for either aerobic activities group. Moreover, women from the combination of aerobic plus resistance exercise group had 13% lower LDL-cholesterol when compared with highly active for either aerobic activities group (P= 0.051).
These data suggest that combining aerobic and resistance-type activities may confer a better effect on lipoprotein profile in healthy individuals than aerobic activities alone.
Pitsavos et al 2009 Resistance exercise plus to aerobic activities is associated with better lipid’s profile among healthy individuals : The ATTICA study. QJMed vol 102 pp 609-616

Fibre to treat the irritable bowel syndrome

This is a very good trial of the use of dietary fibre in the treatment of IBS.
Increasing the intake of dietary fibre (either insoluble or soluble) is a universally advocated for the treatment of irritable bowel syndrome

No previous study on this treatment had been undertaken on its effects in the primary care setting, where the vast majority of these patients are managed
The objective of this randomised blind trail was determine the effectiveness of increasing the dietary content of soluble fibre (psyllium) or insoluble fibre (bran) in patients with irritable bowel syndrome in a General practice setting with 275 patients aged 18-65 years with irritable bowel syndrome.
The trial was 12 weeks of treatment with 109 psyllium (n=85), 10 g bran (n=93), or 10 g placebo (rice flour) (n=93).
The primary end point was adequate symptom relief during at least two weeks in the previous month, analysed after one, two, and three months of treatment to assess both short term and sustained effectiveness. Secondary end points included irritable bowel syndrome symptom severity score, severity of abdominal pain, and irritable bowel syndrome quality of life scale.
The proportion of responders was significantly greater in the psyllium group than in the placebo group during the first month (57% v35%; relative risk 1.60,95% confidence interval 1.13 to 2.26) and the second month of treatment (59% v 41 %; 1.44, 1.02 to 2.06).
Bran was more effective than placebo during the third month of treatment only (57% v 32%; 1.70, 1.12 to 2.57), but this was not statistically
After three months of treatment, symptom severity in the psyllium group was reduced by 90 points, compared with 49 points in the placebo group (P=0.03) and 58 points in the bran group (P=0.61 versus placebo). No differences were found with respect to quality of life. Fifty four (64%)
of the patients allocated to psyllium, 54 (56%) in the bran group, and 56 (60%) in the placebo group completed the three month treatment period. Early dropout was most common in the bran group; the main reason was that the symptoms of irritable bowel syndrome worsened.

Bijkerk et al 2009 Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial.
BMJvol 339 pp 613-615

My own practice was a mix of the two forms of fibre, bran for breakfast and an apple and an orange a day.

complications of obesity

Relative risks of obesity

Greatly increased risk ( > 3)

Metabolic

Type 2 diabetes, gallbladder disease. hypertension, dyslipidaemia, insulin

resistance, non-alcoholic fatty liver

Direct effect

Sleep apnoea, breathlessness, asthma, social Isolation, depression, daytime

sleepiness/fatigue

Moderately increased risk( 2-3)

Metabolic

Coronary heart disease, stroke, gout
Direct effect
Osteoarthritis, respiratory disease, hernia, psychogical problems

Moderately increased risk (1-2)

Metabolic

Cancer, impaired fertility, polycystic ovaries, skin complications, cataract.

Direct effect
Varicose veins, musculoskeletal problems, backache, stress incontinence, oedema/cellulitis

Leff and Heath 2009 Surgery for obesity in adulthood BMJ vol 339 pp 740-746
Mokdad et al 2001 Prevalence of obesity and obesity related health risk factors JAMA
2003, 289: 76-9

Surgical treatment of obesity in adults

Obesity is a health hazard.
Leff and Heath in a review in British Medical Journal 26 Sept 2009 p 740-746 state
The surgical treatment of obesity can only be proposed if
1. the BMI ( kg/m2) over 40
unless they have co-existing type 2 diabetes, high blood pressure or sleep apnoea when 35-40 suffices.
2. failed to significantly loose weight over at least 6 months.
3. the surgery has to take place in an experienced equipped unit for pre operative, operative and post operative care.
4. fitness for surgery

That bariatric surgery is the only long term solution for such morbid obesity. Common procedures for weight loss include gastric banding, Roux –en –Y bypass and sleeve gastrectomy.
Careful follow up subsequently is important and includes vitamin and mineral supplements. Following Roux –en –Y bypass vitamin B12 supplements are obligatory.
Leff and Heath 2009 Surgery for obesity in adulthood. British Medical Journal 26 Sept p 740-746
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Wheat and biofuels in UK

Britain has been self sufficient in wheat for ever. Sufficient is grown ( 14 m tonnes in 2009). However there are new factors affecting this sufficiency.
A biofuel refinery in Wilton North Tees will consume one tenth of the British wheat production. Which shaves off the flexibility from our wheat resources.The wheat that is used is the low quality wheat used for animal feed. The facility will require 1.2 million tonnes of wheat to produce 450 million tonnes of bioethanol . This is because of the Renewable Transport Fuel Obligation which requires 5% of all vehicle fuel to come from biofuels by 2014.The facility will also produce 350,000 tonnes of high protein animal feed. This will significantly reduce the import of soy-based feed imported from Brazil grown on cleared forest land. The effects on the food chain and displacement chain are not apparent at the moment
Times Monday 5 October 2009 p 43. Robin Pagnamenta.